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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 31  |  Issue : 5  |  Page : 226-232

Does stone analysis have better predictive value than urine culture and stone culture for predicting systemic inflammatory response syndrome post retrograde intra renal surgery? A single center pilot study


Department of Urology, Minimal Access Surgery Training Institute, Shyam Urosurgical Hospital, Ahmedabad, Gujarat, India

Date of Submission24-Apr-2020
Date of Decision30-May-2020
Date of Acceptance25-Aug-2020
Date of Web Publication27-Oct-2020

Correspondence Address:
Ravi J Jain
Department of Urology, Minimal Access Surgery Training Institute, Shyam Urosurgical Hospital, Viva Complex, 4th Floor, Opposite Parimal Garden, Ellisbridge, Ahmedabad - 380 006, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/UROS.UROS_46_20

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  Abstract 


Purpose: Infective complications such as fever, systemic inflammatory response syndrome (SIRS), septicemia, and shock are common and preventable complications after retrograde intrarenal surgery (RIRS). Patients with positive urine and stone cultures have a greater risk of SIRS. Infection stones (carbonate apatite) are bacteria-harboring stones that predispose to sepsis. A pilot study is conducted to establish the role of stone analysis in predicting SIRS after RIRS compared to urine and stone cultures. Materials and Methods: Sixty patients who underwent RIRS from January 2018 to June 2018 were prospectively evaluated with respect to preoperative urine culture, stone burden and location, operative time, postoperative clinical course, residual stone size, stone culture, stone analysis, and occurrence of septicemia-related events. Results: 5 out of 60 patients who underwent RIRS developed SIRS (8%). Sensitivity levels of predicting SIRS were different, where urine culture (20%), stone culture (20%), and carbonate apatite on the stone analysis (60%). Positive urine culture and stone culture had no significant relation to the prediction of SIRS (P = 1). Carbonate apatite was present in 12 samples (20%) in varying proportions. The presence of apatite >50% of the total sample was in 5/60 samples (8%), which are referred to as infection stones. Three out of these 5 patients with infection stones developed SIRS (60%). Thus, the presence of carbonate apatite in the stone analysis had a statistically significant relation to SIRS (P < 0.01). Conclusion: The presence of carbonate apatite >50% on stone analysis has higher sensitivity than urine and stone culture in predicting SIRS after RIRS.

Keywords: Carbonate apatite, infection stone, retrograde intrarenal surgery, sepsis, stone culture, systemic inflammatory response syndrome, urine culture


How to cite this article:
Parikh KP, Jain RJ, Parikh AK. Does stone analysis have better predictive value than urine culture and stone culture for predicting systemic inflammatory response syndrome post retrograde intra renal surgery? A single center pilot study. Urol Sci 2020;31:226-32

How to cite this URL:
Parikh KP, Jain RJ, Parikh AK. Does stone analysis have better predictive value than urine culture and stone culture for predicting systemic inflammatory response syndrome post retrograde intra renal surgery? A single center pilot study. Urol Sci [serial online] 2020 [cited 2020 Nov 30];31:226-32. Available from: https://www.e-urol-sci.com/text.asp?2020/31/5/226/299261




  Introduction Top


Retrograde intrarenal surgery (RIRS) is the first-line modality of treatment for renal and upper ureteric stones <2 cm size.[1] Infective complications such as fever, systemic inflammatory response syndrome (SIRS), septicemia, and shock are known post-RIRS complications with an incidence rate of 1.7%–18.8%.[2],[3] The risk factors for high septicemia rates in RIRS are the high intra-pelvic pressures, operative duration, positive urine, and stone cultures, presence of infection stones, improper sterilization, and lack of aseptic precautions.[4] Many research papers support the correlation between positive urine culture, stone culture, and the risk of sepsis.[5],[6],[7] Struvite stones (magnesium ammonium phosphate) have been classically known as stones forming in the presence of infected urine.[8] Carbonate apatite-containing stones have also been known to harbor bacteria within the stone and are called infection stones. These apatite stones too have the risk of developing sepsis.[9] A pilot study is devised to find out the role of stone analysis in predicting SIRS after RIRS.


  Materials and Methods Top


This study aims at evaluating the correlation of postoperative SIRS with positive urine culture, positive stone culture, and the presence of carbonate apatite on stone analysis. This was to search for a surrogate marker which could help in reaching a better prediction of SIRS after RIRS.

Ethics

The study protocol was approved by the scientific and ethics committee of the hospital. All patients were counseled preoperatively about the merits and demerits of RIRS, and informed consent was taken.

Study design

This was a prospective single-center study conducted from January 2018 to June 2018 comprising 60 patients who underwent RIRS for renal and/or upper ureteric stones.

Inclusion criteria

Patients with

  • Age >18 years
  • Single/multiple renal and/or upper ureteric stones
  • Stone burden ranging from >5 mm to <35 mm
  • Patients with no history or previous history of Ureterorenoscopy (URS), per cutaneous nephrolithotripsy (PCNL) or extracorporeal shock-wave lithotripsy, both were included
  • Anatomically, abnormal kidneys such as solitary kidney and horse-shoe kidney.


Exclusion criteria

  • Pediatric patients <12 years
  • Staghorn calculi with stone burden >35 mm
  • Comorbidities such as diabetes, hypertension, and ischemic heart disease
  • Patients with lower ureteric stones.


Preoperative workup included urine routine and microscopy, culture and sensitivity, hemogram, serum creatinine, coagulation profile, and noncontrast computed tomography of kidney ureter bladder (NCCT KUB). Mid-stream urine was collected in a sterile container, examined for gram staining and inoculated on Mac–Conkey agar and incubated at 37°C for 24 h. In the case of positive culture, colony count was done, and antibiotic culture sensitivity was done using the disc-diffusion method (Kirby and Baur method).[10],[11] Sterile urine culture was mandatory before the procedure. In case of positive urine culture, culture-specific antibiotics were given for 5 days preoperative, repeat urine culture was sent, and then, RIRS was performed. The 2nd generation of cephalosporin is the antibiotic of choice. All endoscopes and instruments were sterilized with the plasma sterilization. The stone burden was calculated as the longest dimension of a single stone or the mean size of multiple stones. Stone hardness was measured with Hounsfield value on NCCT KUB.

Routinely, we do not prestent patients for RIRS. Prestenting is done in cases with febrile urinary tract infection (UTI) or when the ureter was too tight and the procedure needed to be staged; in such cases, these patients were excluded from the study. Cysto-urethroscopy followed by semi-rigid 4.5 French (Fr) Ureterorenoscopy (URS) was done. Balloon dilatation was required for narrow ureteric orifice or tight ureter. Then a ureteric access sheath (UAS) of 9.5 Fr/11.5 Fr was back-loaded over the guidewire in all cases. Since literature suggests that UAS is protective against pyelovenous and pyelolymphatic backflow, significantly reducing the intra-pelvic pressures, this could contribute to lower infection rates after RIRS.[12] Hence, in the present study, cases in which UAS could not be placed were excluded.

First, all the calyces were inspected and the stone location, number, and size were assessed. Next, stone dusting with Holmium: YAG laser was performed. The settings were 0.6–0.8 J and 10–15 Hz, and stones were adequately dusted. Once the stone was pulverized, all calyces were re-checked, and retrograde pyelography was performed to rule out ureteric or fornyceal perforation. Finally, few stone fragments were collected and sent for stone culture and analysis in separate sterile containers. Double J Stent was placed in all patients as our routine protocol.

Postoperatively, patients were monitored for hematuria, flank pain, and signs of septicaemia such as fever, chills, or hypotension. Hemogram was performed in case of suspicion of SIRS to look for raised leukocyte count. Injectable antibiotics were continued till the submission of fever in such cases. All patients were discharged after 36–48 h and were followed up with NCCT KUB after 4 weeks. Re-RIRS was performed for a clinically significant residual fragment of size >3 mm. Double-J stent was removed under local anesthesia in case of complete clearance.

Stone fragments collected were crushed and cultured in 5 ml thioglycolate broth which was incubated at 37°C for 18–24 h. Subcultures were made on blood agar and Mac Conkey's agar plate and incubated at 37°C for 24 h. The growth from the culture plates was examined for the number of colonies from the wash and crush fluids of calculus. Antibiotic sensitivity was done using the Kirby–Baur method.[10],[11],[13]

For stone analysis, pulverised stones were examined by Fourier transform infra-red spectroscopy (FTIR).[14],[15] In this technique, the background spectrum is measured initially with no sample in contact with the attenuated total reflectance unit of the Nicolet iS5 FT-IR spectrometer (Thermo Fisher Scientific Inc., Waltham, MA, USA). Around 2 mg of powdered kidney stone constituents was applied to the flat surface of the crystal of the spectrophotometer and spectra were collected with the help of Thermo Scientific OMNIC software (Thermo Electron Corporation, Madison, WI, USA) from 2000 to 450 cm − 1. The unknown spectra generated by FT-IR were compared using 756 synthetic kidney stone spectra in the NICODOM library. Visual examination of each spectrum was done to select the best fitting spectra with their matching percentage. Reports were generated on the stone components that gave details of the chemical name, mineral name, and chemical formula. Struvite stone was identified as Magnesium Ammonium Phosphate stone. Carbonate apatite stones were identified as stones with apatite content >50% in the absence of struvite.[9]

The occurrence of fever postoperatively is defined as an increase in the body temperature to >38°C, which persisted for 48 h. The definition of sepsis has been changing from time to time in the literature. According to the 1991 consensus conference, sepsis-1 was defined and four SIRS criteria were identified as:

  • Tachycardia (heart rate >90 beats/min)
  • Tachypnea (respiratory rate >20 breaths/min)
  • Fever or hypothermia (temperature >38 or <36°C)
  • Leukocytosis, leukopenia, or bandemia (white blood cells >1200/mm3, <4000/mm3 or bandemia ≥10%).


Patients who met two or more of these criteria fulfilled the definition of SIRS and Sepsis-1 was defined as infection or suspected infection leading to the onset of SIRS.[16] A 2001 task force recognized the limitations with these definitions and expanded the list of diagnostic criteria, resulting in the introduction of sepsis-2.[17] This was again revised and redefined as sepsis-3 in 2016 by a task force convened by national societies including the Society of Critical Care Medicine and the European Society of Intensive Care Medicine.[18]

This new definition abandoned the use of SIRS criteria in identifying sepsis and defines sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection. They described a simplified method termed “quick SOFA” to facilitate easier identification of patients potentially at risk of dying from sepsis. This score is a modified version of the Sequential (Sepsis-related) Organ Failure Assessment score (SOFA). A qSOFA score of ≥ 2 points indicates organ dysfunction [Table 1].[18],[19] Although the new qSOFA criteria are specific and easy to calculate, they have a low level of sensitivity, which likely excludes their use as a screening tool for early sepsis when the treatment is most effective.[20] Thus, whether to use the old definition of sepsis-1 as defined by SIRS criteria or the new sepsis-3 definition as defined by qSOFA criteria, still needs further research.[20],[21] Due to the lack of appropriate guidelines, the current study followed the Sepsis-1 definition, and patients with SIRS after RIRS have been identified. The present study basically aims at determining the role of stone analysis in predicting SIRS after RIRS.
Table 1: Quick sequential (sepsis-related) organ failure assessment score criteria

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Statistics

Statistical analysis was done under expert statistician's guidance using SPSS Version 20, International Business Machines Corp. (IBM Corp.), Chicago USA. Qualitative data are presented as frequency as well as in the percentage form. Fisher's exact test has been used for carrying out statistical significance value. P < 0.05 is considered to be statistically significant between the groups.


  Results Top


Demography and stone distribution is demonstrated in [Table 2]. 38 (64%) out of 60 patients, who underwent RIRS, had stone burden <1.5 cm; whereas 22 (36%) of patients had stone burden >1.5 cm. Nine (15%) patients had a previous history of urolithiasis. The mean operative duration was 39 min (15–90 min). On follow-up at 4 weeks with NCCT KUB, 6 (10%) patients had residual stones, out of which 4 patients (6.6%) required a second procedure. The mean residual stone size was 8 mm.
Table 2: Demographic data of patients

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The incidence of SIRS was noted in 5/60 (8%) patients. No patient developed septicemic shock or required intensive care unit admission. Preoperative urine culture was positive in 15/60 (25%) patients and 1/5 (20%) patients with SIRS. The stone culture was positive in 10/60 (17%) patients and 1/5 (20%) patients with SIRS. According to the current study, positive urine and stone culture had no significant relation to the prediction of SIRS (Fischer's exact t-test, P = 1) [Table 3].
Table 3: Statistical correlation between urine culture, stone culture, and presence of apatite stone (infection stone) on stone analysis with the incidence of systemic inflammatory response syndrome postretrograde intra renal surgery

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Stone analysis report showed all stones to be mixed stones. The most predominant component was calcium oxalate monohydrate in 51/60 (85%) reports, followed by calcium oxalate dihydrate in 3/60 (5%), and uric acid in 1/60 (<2%) reports. Struvite (Magnesium Ammonium Phosphate) was not seen in any of the samples. Carbonate apatite (mineralogical name) or Dahllite (chemical name) was present in varying proportions in 12/60 samples (20%) with its content >50% of the total sample in 5/60 samples (8%). We refer to these five cases with apatite content >50% as infection stones [Figure 1] and [Figure 2].
Figure 1: Fourier transform infrared spectroscopy analysis of a patient showing carbonate apatite as the main stone content

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Figure 2: Fourier transform infrared spectroscopy analysis of another patient showing carbonate apatite as the main stone content

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Carbonate apatite (infection stone) was positive in 5/60 (8%) patients and 3/5 (60%) patients with SIRS. This test has 60% sensitivity and 96% specificity. Positive predictive value is 60% and negative predictive value is 96% [Table 4]. As per the current study, the presence of carbonate apatite stone has a statistically significant relation to the presence of SIRS (P < 0.01, Fischer's exact t-test).
Table 4: Sensitivity, specificity, positive predictive, and negative predictive value of urine culture, stone culture and apatite stone presence on stone analysis for predicting systemic inflammatory response syndrome postretrograde intra renal surgery

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Escherichiacoli was the most common organism isolated in both urine and stone cultures, followed by Klebsiella and Pseudomonas in 1 patient, respectively. Stone culture and urine culture both were positive in 6/60 (10%) cases with a similar organism and antibiotic sensitivity, and no such patient showed the signs of SIRS. Positive stone culture with negative urine culture was observed in 4/60 (7%) patients. Positive urine culture with negative stone culture was observed in 9/60 (15%) patients. No such patient showed the signs of SIRS.


  Discussion Top


RIRS today is the first-line modality for managing stones <2 cm and 2nd line modality after PCNL for lower calyx stones and stone burden >2 cm.[1] The relatively lower morbidity of RIRS as compared to PCNL raised the popularity of this surgery.[22] However, septicemia is a known and dreaded complication following RIRS. The incidence rate of postoperative infectious complications ranges from 1.7% to 18.8%.[2]

Risk factors that can lead to septicemia post endourological procedures include UTI, high intra-pelvic pressures, improper sterilization, and immuno-compromised statuses such as comorbidities such as diabetes mellitus and chronic kidney disease,.[4] By addressing these issues independently, we can significantly reduce septic complications and safely render endourological procedures. UTI is a known risk factor in stone bearing patients responsible for postprocedure sepsis. Mid-stream urine culture is the conventional way of urine analysis preoperatively. Techniques of urine culture on blood agar, Mac Conkey Agar, and antibiotic sensitivity using Kirby–Baur method are well known.[7],[10],[11] However, mid-stream urine cultures are shown to have low levels of sensitivity in the current study (10%) which agrees with other studies.[5],[6],[7] It has already been proven that renal pelvic urine culture has better sensitivity than mid-stream urine culture in predicting postoperative sepsis.[23]

Stone cultures are also similarly done as urine culture and antibiotic sensitivity by Kirby–Baur method. Stone culture has been widely studied in relation to postoperative sepsis. The poor co-relation between preoperative urine culture and stone culture has been documented.[23] Few authors have not found any positive co-relation between stone culture and sepsis and did not change the antibiotic based on stone culture.[24] However, other authors have found a positive correlation between stone culture and postoperative sepsis.[5],[6],[7] The current study sheds light upon the low sensitivity of stone culture (20%) in predicting SIRS as compared to (81%) reported by Devraj et al. where (P < 0.01).[5]

Stone analysis techniques include chemical tests, X-ray diffraction, infra-red spectroscopy techniques including FT-IR spectroscopy, and Raman spectroscopy. The Guidelines on Urolithiasis of the European Association of Urology recommend infrared spectroscopy or X-ray diffraction for kidney stone analysis. FTIR today has become the method of choice for stone analysis.[14]

Historically, renal calculi associated with UTI have been identified by the presence of struvite (magnesium ammonium phosphate) in the mineral composition of the stone.[25],[26] Urea splitting organisms such as Proteus, Pseudomonas, Klebsiella, etc., split the urea in urine to produce ammonia, which renders the urine alkaline. In this alkaline environment, there is a crystallisation of ammonium magnesium phosphate (triple phosphate).[27],[28] Struvite stones are known to be associated with the risk of sepsis postsurgery.[8] However, many urinary stones including struvite stones also contain calcium phosphate in the mineral form of apatite. This mineral retains imprints of bacteria suggesting it is a potential source for retention of infectious agents that could be released during the surgery.[29] Moreover, the number of bacterial imprints in apatite has shown a correlation with the carbonate content of the mineral. High carbonate content in apatite is consistent with the mineral being formed in the presence of infection.[29],[30]

Fan et al. noted in their study that infectious stones were a risk factor for developing SIRS.[4] He mentioned carbonate apatite, magnesium ammonium phosphate, and struvite stones as infectious stones. However, they found the incidence of infectious complications among patients with infectious struvite stones to be higher than that of patients with other stones (5/13, 38.46% vs. 14/214, 6.54%; P < 0.05). The incidence of infection among carbonate apatite stones was not studied or mentioned.

Englert used FTIR spectroscopy to study the correlation between stone culture, struvite stones, and apatite stones on stone analysis.[9] They concluded that stone culture was positive in 73% of struvite stones and 65% of apatite stones. However, 27% of struvite stones and 35% of apatite stones showed no culturable organism in their stones. Hence, stone composition alone was not a perfect indicator of culturable organisms in the stones. Carpentier et al. also concluded that a greater number of bacteria in the urine would yield a higher carbonate content in the apatite mineral.[29] In the current study too, only 1 out of 5 carbonate apatite stones had a positive stone culture.

The published data on the incidence of SIRS after RIRS is 7.7% (Berardinelli et al.),[3] 17% (Li etal.),[31] and 6% (Parikh et al.) where (P<0.01).[32] Low septicemia rate is attributed to strict aseptic precautions, negative urine cultures, low intra-pelvic pressures (due to UAS and controlled irrigation system), plasma sterilization of all flexible, digital, and semi-rigid endoscopes, camera, light cables, and other surgical instruments. In the present study, the high rate of SIRS (8%) is probably attributable to the small number of patients (60) as compared to the published study of 131 patients.[32] Similarly, the increased number of stones with a stone burden >1.5 cm could be a reason for the high SIRS rate in the present study. 11 patients (18%) had stone burden 1.6–2 cm, and 11 patients (18%) had stone burden >2 cm. Large stone burden and longer intraoperative time are the known risk factors for SIRS.[4]

To summarize, poor correlation is found between positive urine culture and sepsis (P = 1), and positive stone culture and sepsis (P = 1); a statistically significant correlation between the presence of apatite stone (infection stone) and sepsis (P < 0.01) was noted [Figure 3]. Thus, stone analysis can be an important test to predict sepsis after surgery. At our center, a stone analysis report is available on the next postoperative day, whereas stone culture is usually available after 48 h if no growth has been observed. Hence, a stone analysis report can be helpful in the early identification of patients susceptible to developing SIRS. Besides, stone analysis can be helpful in dietary management and the prevention of recurrent urolithiasis.
Figure 3: Graphical representation of statistical correlation between urine culture, stone culture, and presence of carbonate apatite on stone analysis with the incidence of systemic inflammatory response syndrome postretrograde intra renal surgery

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The current study was not without limitations. This was a single-center pilot study with a small sample size of patients. Other parameters such as urine analysis, intra-operative pelvic urine culture, bladder urine culture, varying compositions of stone analysis, operative time in relation to the stone burden, intra-pelvic pressures, irrigation pressures, and residual stones need to be evaluated individually in large sample-sized multi-center, prospective studies.


  Conclusion Top


The presence of carbonate apatite >50% in stone analysis has high sensitivity and specificity as compared to urine culture and stone culture in predicting SIRS after RIRS. Hence, stone analysis can be a useful surrogate marker to the prediction of developing SIRS after RIRS.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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