RESULTS
In this prospectively conducted study, no difference was observed between the groups in terms of the mean age, female/male ratio, BMI, presence of DM and stone locations. However, the mean stone dimensions were calculated as 343.65±236.63 mm2and 122.48±51.292 mm2for the PNL and RIRS groups, respectively, indicating a statistically significant difference (p ≤ 0.001) (Table1).
The mean operation time of the patients was 60.25 ± 22.98 and 47.50 ± 20.69 minutes in the PNL and RIRS groups, respectively, and a statistically significant difference was found between the two groups (p ≤ 0.001). The mean length of hospital stay was 4.10 ± 2.37 days in the PNL arm and 1.53 ± 1.61 days in the RIRS arm, also indicating a statistically significant difference (p ≤ 0.001). Stone-free status and presence of CIRFs were accepted as surgical success, and there was no statistically significant difference between the two groups in terms of this outcome. The modified Clavien classification was used for the postoperative complication evaluation. Twenty-six patients (65%) that had undergone RIRS were evaluated as Clavien 0, 12 (30%) patients as Clavien 1, and 2 (5%) patients as Clavien 2 (infection) (22.5%). In the PNL group, Clavien 0 was seen in 9 (22.5%) patients, Clavien 2 in 6 (22.5%) (infection in 4, bleeding in 1, and arteriovenouz fistula in 1), and Clavien 3A in 1 (2.5%) (double-J stent requirement). There was a statistically significant different between the two groups in terms of the Clavien classification (p=0.001) (Table1).
Preoperative hemoglobin, urea, creatinine, GFR, MIOX and KIM-1 levels, no significant difference was observed between two groups.In the PNL arm, the post-operative hemoglobin (12.92 ± 1.37g/dl) was found to be statistically significantly lower than in the RIRS arm (14.98 ± 3.30 g/dl) (p ≤ 0.001) (Table 2).
In the intra-group comparisons, there was no statistically significant difference between the preoperative and postoperative values of hemoglobin urea, creatinine, GFR and KIM-1 in patients that had undergone RIRS; however, the mean MIOX value was increased from 17.80 ± 15.39 ng/ml preoperatively to 25.30 ± 20.11 ng/ml postoperative, and this increase was statistically significant (p = 0.001) (Table 2).Within the PNL group, the hemoglobin value was measured as 14.01 ± 1.34 mg/dl preoperatively and 12.92 ± 1.37 mg/dl postoperatively, indicating a statistically significant difference (p ≤ 0.001). Similarly, in this group, the preoperative and postoperative KIM-1 values ​​were 1.21 ± 0.44 and 1.68 ± 0.58 ng/ml,respectively, and the preoperative and postoperative MIOX values were 15.23±9.36 ng/ml and 25.81±16.13 ng/ml, respectively showing a statistically significant difference (p ≤0.001 for both). No significant difference was observed in terms of the other variables ​​(Table 2). In the intra-group evaluation for the postoperative and preoperative differences, the mean MIOX increase was calculated as 7.501 ± 16.46 ng/ml for the RIRS group and 10.583 ± 9.73 ng/ml in the PNL group, and there a statistically significant difference between the two groups in favor of the latter (p = 0.001). Similarly, while the mean KIM-1 increase was 0.375 ± 1.13 ng/ml in the RIRS group, it was 0.471 ± 0.328 ng/ml in the PNL group, indicating a statistically significant difference (p = 0.003) (Table 2).
DISCUSSION
Urinary system stone disease is a pathology that constitutes an important part of urology practice. The treatment of kidney stone disease has changed significantly, especially in the last two decades, with the improvement of tools and reduction in their size due to the development of technology. ESWL, PNL and RIRS are considered as three main treatment methods for the treatment of upper urinary stone disease [13].
PNL is recommended as the preferred minimally invasive method due to its high success rates in patients with a high stone burden (>20mm) and complex stones [5]. However, complications, such as hemodynamic impairment, vascular bleeding, and parenchymal bleeding, and acute kidney injury may occur after the operation [14].In recent years, with the technological advances in endourological equipment and increasing surgeon experience, RIRS presents as an alternative to PNL, with lower complication rates [15; 16]. There are publications that consider RIRS to be a very good minimally invasive treatment alternative for intrarenal stones of <20 mm and report high stone-free rates even in larger stone sizes [17; 18].
During surgical operations for kidney stones, there may be certain damage to the kidneys. Having knowledge of the extent of injury caused by each technique used can guide surgeons in the selection of both patients and surgical techniques. Creatinine is used in daily practice to show kidney injury. However, creatinine is a non-specific marker affected by various factors, including age, gender, muscle density, and liver function. In addition, creatinine levels increase days after kidney damage occurs by which time 50% or more of renal function is lost [19]. Therefore, new molecules have been used to reveal kidney injury more specifically at an earlier stage. In an experimental animal model investigating one of these molecules, KIM-1, the urine and plasma levels were measured after inducing ischemic kidney injury. It was found that the plasma KIM-1significantly increased at the third hour compared to the preoperative levels and remained at a high level until the 96th hour [20]. In the same study, it was shown that the plasma KIM-1 level was correlated with urine the KIM-1 level and significantly higher in individuals with kidney injury compared to healthy individuals. Many studies have evaluated urine KIM-1 levels; however, to the best of our knowledge, there is no study in the literature investigating the role of plasma KIM-1 molecule in revealing possible damage of kidney stone surgery.
In a previous study, the diagnostic sensitivity and specificity of the MIOX molecule released from the proximal tubules of kidneys in showing acute kidney injury were observed as 53.8% and 81.5%, respectively. Accordingly, it was concluded that MIOX could be used as a marker of acute kidney injury [21]. In addition, when compared to creatinine, MIOX was observed to increase much earlier in case of kidney injury [21].However, a review of the literature shows no study comparing the MIOX molecule in patients that have undergone PNL and RIRS.
In our study, the stone volume of the PNL group was statistically significantly higher than that of the RIRS group (p <0.001). This difference was due to the indication of PNL for stones with a larger volume, as recommended in the EAU 2019 urinary system stone disease guidelines. In addition, the operation time was significantly longer in the PNL group (60.25 ± 22.98 min) compared to the RIRS group (47.50 ± 20.69 min) (p ≤ 0.001). We also consider this to be related to the different stone volumes. Similarly, in other studies comparing PNL and RIRS, the stone volume was observed to be higher and the operation time was longer operation times in the former [13; 22]. However, in a study in which the stone sizes were similar in the two surgery groups, the RIRS duration was found to be longer in lower pole stones [23]. The main reason for the prolongation of this period may be due to the more difficult manipulation of the flexible ureteroscope in lower pole stones. In our study, the length of hospital stay was 4.10 ± 2.37 days in the PNL group and 1.53 ± 1.61 days in the RIRS group, indicating a statistically significantly longer value for the former (p ≤ 000.1), which is consistent with the literature [13; 22; 23].
In this study, the operative success rates were 92.5% and 90% in the PNL and RIRS arms, respectively, and no statistical difference was observed between them. The success rates of the studies in the literature were also similar. However, the postoperative stone-free rates are affected by clinical parameters, such as stone location, obesity, stone size, stone composition and anatomy of the renal calyces. There are studies reporting 77% to>90% success rates in RIRS whereas for PNL, the success rates for lower pole stones of 1-2 cm and above 2 cm are given as 92% and 86%, respectively [25]. While two studies [26; 27] showed a higher stone-free rate in the PNL group (92 and 98%, respectively) than the RIRS group (89 and 95%, respectively), another study showed a statistically non-significant higher stone-free rate in the RIRS group compared to the PNL group [28]. Lastly, Mehmet et al. determined the stone-free rates as 91.4% and 87% in the PNL and RIRS groups, respectively [13].
We used the modified Clavien classification to evaluate the complications and found the rate of complications to be statistically significantly higher in the PNL arm (p = 0.001). Similar to our results, the literature contains studies indicating a higher rate of complications in the PNL arm than in the RIRS arm [23; 28]. While no major complications were observed in our study, 2 (5%) patients in the PNL arm required blood transfusion. Post-operative fever occurred in 7 patients (17.5%) in the PNL arm and 2 (5%) patients in the RIRS arm.
In a review reported the most common complications of PNL as extravasation (7.2%), bleeding requiring blood transfusion (11.2 - 17.5%), and fever (21 - 32.1%) while rare major complications included septicemia (0.3 - 4.7%), colon injury (0.2 - 4.8%), and pleural injury (0 - 3.1%) (24).
In our study, while there was no difference between the preoperative and postoperative hemoglobin values in the RIRS arm, the postoperative hemoglobin was statistically significant lower compared to the preoperative value in the PNL arm (p ≤ 0.001). GyooHwan Jung et al. reported similar data to our results.
In a previous study conducted with RIRS patients, it was observed that MIOX did not increase in the postoperative period [29]. In contrast, the postoperative values ​​of the MIOX molecule statistically significantly increased in our PNL group. The preoperative and postoperative MIOX levels in the RIRS arm were 17.80 ± 15.3 and 25.30 ± 20.11ng/ml, respectively, and we found a statistically significant increase in this parameter (p = 0.001). However, the increase in the MIOX values was 10.583 ± 9.73ng/ml in the PNL group versus 7.501 ± 16.46ng/ml in the RIRS arm, indicating a statistically significantly higher increase in the former (p = 0.001) (Table 2).
In this study, although there was an increase in the plasma KIM-1 levels in the RIRS arm in the postoperative period, no statistically significant difference was observed. However, the postoperative KIM-1 value in the PNL arm was found to be statistically significantly higher than the preoperative value. Our findings our supported by Balasar et al.[30], who compared PNL, RIRS and mini-PNL, and found an increase in the KIM-1/creatinine values ​​in the PNL and RIRS arms in the postoperative period, and this increase was statistically significantly higher in the PNL group.
We detected a statistically significant increase in both the KIM-1 and MIOX values ​​in the postoperative period among the patients that had undergone PNL. In the RIRS group, this increase was observed only in MIOX. We showed that acute kidney injury occurred in both surgical methods; however, it was greater in PNL.
Limitations
The limitations of this study include the relatively low number of the patients in our sample and a single blood sample collection in the postoperative period.
CONCLUSION
In the comparison of the patients that underwent PNL or RIRS, we first demonstrated that acute kidney injury could be detected using the MIOX and plasma KIM-1 molecules, and the increase in these molecules was higher in the PNL arm. The higher increase in the PNL arm suggests that this method causes greater acute kidney injury than RIRS; however, there is a need for further studies with larger case series to support our data.
1. Jungers P, Joly D, Barbey et. al. F: ESRD caused by nephrolithiasis: prevalence, mechanisms, ant prevention. J. Kidney Disease. Vol. 44: 799, 2004
2. Goodwin We, Casey Wc, Woolf W. et al. Percutaneous trocar (needle) nephrostomy in hydronephrosis. J Am Med Assoc. 1955 Mar 12;157:891-4..
3. Fernström I, Johansson B. Percutaneous pyelolithotomy. A new extraction technique. Scand J Urol Nephrol. 1976;10(3):257-9
4. Mahmoud Osman , Gunnar Wendt-Nordahl, Katrin Heger et al. Percutaneous nephrolithotomy with ultrasonography‐guided renal access: experience from over 300 cases. BJU international, 96(6), 875-878
5. C.Türk (Chair), A.Neisus, A. Petrik et al. EAU Guidelines on Urolithiasis. 2019.
6. Nakada SY, Pearle MS. Ureteropyeloscopy. Conlin MJ; Advanced Endourology. Humana Pres Inc, pp 105-108, 2006
7. Charles G Marguet , W Patrick Springhart, Yeh H Tan et al. (2005). Simultaneous combined use of flexible ureteroscopy and percutaneous nephrolithotomy to reduce the number of access tracts in the management of c. BJU international
8. Justin Westhuyzen, Zoltan H Endre, Graham Reece et al. (2003). Measurement of tubular enzymuria facilitates early detection of acute renal impairment in the intensive care unit. Nephrology Dialysis Transplantation, 18(3), 543.
9. Sushrut S, Waikar J, Bonventre V. Biomarkers for the Diagnosis of Acute Kidney Injury. Nephron Clin Pract 2008;109:c192–c197..
10. Venkata S Sabbisetti , Sushrut S Waikar , Daniel J Antoine et al.(2014). Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes. J Am Soc Nephrol . 2014 Oct;25(10):2177-86
11. Kushlinskii NE, Gershtein ES, Naberezhnov DS et al. Kidney Injury Molecule-1 (KIM-1) in Blood Plasma of Patients with Clear-Cell Carcinoma. Bull Exp Biol Med . 2019 Jul;167(3):388-392.
12. Gaut JP, Crimmins DL, Ohlendorf MF et al. Development of an immunoassay for the kidney-specific protein myo-inositol oxygenase, a potential biomarker of acute kidney injury. Clin Chem . 2014 May;60(5):747-57.
13. Berkan Resorlu , Ali Unsal, Tevfik Ziypak et al. Comparison of retrograde intrarenal surgery, shockwave lithotripsy, and percutaneous nephrolithotomy for treatment of medium-sized radiolucent renal Stones. World J Urol.
14. Egilmez, Tulga Goren, Mehmet Resit . Predicting surgical outcome of percutaneous nephrolithotomy: validation of the guy’s stone score and nephrolithometric nomogram in terms of success and complications. J Clin Anal Med 2015; 6(3): 281–286..
15. Maurice Stephan Michel , Lutz Trojan, Jens Jochen Rassweiler Complications in percutaneous nephrolithotomy. Eur Urol 2007; 51: 899-906.
16. Unsal A, Resorlu B, Atmaca AF et al. Prediction of morbidity and mortality after percutaneous nephrolithotomy by using the charlson comorbidity index. Urology 2012; 79: 55-60.
17. Mariani AJ. Combined electrohydraulic and holmium: YAG laser ureteroscopic nephrolithotripsy of large (greater than 4 cm) renal calculi. J Urol 2007; 177: 168-73.
18. El-Anany FG, Hammouda HM, Maghraby HA. Retrograde ureteropyeloscopic holmium: YAG laser lithotripsy for large renal calculi. BJU Int 2001; 88: 850- 3.
19. John A Kellum and Norbert Lameire, Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl 2012; 2(1): 1–138..
20. Venkata S Sabbisetti, Sushrut S Waikar, Daniel J Antoine et al., Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes. Journal of the American Society of Nephrology, 25(10), 2177-2186. 2014.
21. Cuma Mertoglu, Murat Gunay, Ali Gurel et al. Myo-Inosıtol Oxygenase As A Novel Marker In The Dıagnosıs Of Acute Kıdney Injury. J Med Biochem 37: 1–6, 2018.
22. Abdullah Erdoğan, Ercüment Keskin, Abdulsemet Altun, Percutaneous nephrolithotomy versus flexible ureteroscopy in terms of cost-effectiveness in patients with 10-30 mm renal stones. Urologia . 2020 Feb;87(1):41-46.
23. Kursad Zengin, Serhat Tanik, Nihat Karakoyunlu et al., Retrograde Intrarenal Surgery versus Percutaneous Lithotripsy to Treat Renal Stones 2-3cm in Diameter. Biomed Res Int . 2015;2015:914231.
24. Michel MS, Trojan L, Rasweiler JJ. Complications in percutaneous nephrolithotomy. Eur Urol 2007; 51: 899-906.
25. D M Albala, D G Assimos, R V Clayman et al, . Lower pole I: A prospective randomized trial of extracorporeal shock wave lithotripsy and percutaneous nephrostolithotomy for lower pole nephrolithiasis-initial results. J Urol 2001; 166: 2072-80.
26. Akman T, Binbay M, Ozgor F et al. Comparison of percutaneous nephrolithotomy and retrograde flexible nephrolithotripsy for the management of 2-4 cm stones: a matched-pair. BJU Int . 2012 May;109(9):1384-9.
27. Jeong CW, Jung JW, Cha WH et al. Seoul National University renal stone complexity score for predicting stone-free rate after percutaneous nephrolithotomy. PLoS One. 2013;8:e65888.
28. Gyoo Hwan Jung, Jae Hyun Jung, Tae Sik Ahn et. al., Comparison of retrograde intrarenal surgery versus a single- session percutaneous nephrolithotomy for lower-pole stones with a diameter of 15 to 30 mm: A propensity score-matching study. Korean J Urol 2015;56:525- 532.
29. Mertoglu C, Bozkurt A, Keskin E et al. Evaluation of the effect of Retrograde Intrarenal Surgery with Myo-Inositol Oxygenase. Pak J Med Sci. 2018;34(1):170-174..
30.Balasar M, Piskin M.M, Topcu C at all. Urinary kidney injury molecule-1 levels in renal stone patients. World J Urol 2016 Sep;34(9):1311-6..