Analysis of the therapeutic effect of holmium laser intervention on patients with complicated kidney stones and the relationship between serum LncRNA TapSAKI, MCP-1,IL-6 and prognosis of patients

doi:10.21203/rs.3.rs-2216564/v1

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Analysis of the therapeutic effect of holmium laser intervention on patients with complicated kidney stones and the relationship between serum LncRNA TapSAKI, MCP-1,IL-6 and prognosis of patients

https://doi.org/10.21203/rs.3.rs-2216564/v1

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Backgroud: In order to analyze the therapeutic effect of holmium laser intervention on patients with complicated kidney stones and the relationship between serum LncRNA TapSAKI, MCP-1,IL-6 and prognosis of patients, the clinical efficacy of holmium laser interventional Minimally Invasive Percutaneous Nephrolithotomy (mPCNL) for patients with complicated kidney stones is investigated.

Methods: A total of 116 patients with complicated kidney stones admitted to the Department of Urology of our hospital from June 2020 to June 2021 for surgical intervention are selected. Holmium laser combined with mPCNL and open nephrolithotomy group are established according to different surgical intervention methods, and the differences of serum LncRNA TapSAKI, MCP-1 and IL-6 indexes are observed.

Results: Pearson correlation coefficient is used to analyze the correlation between serum LncRNA TapSAKI and MCP-1 and IL-6 in patients with complicated kidney stones. Pearson correlation coefficient analysis shows that serum LncRNA TapSAKI is significantly positively correlated with MCP-1 and IL-6 in patients with complicated kidney stones.

Conclusion: It is clearly evident that Holmium laser combined with mPCNL in the treatment of complicated kidney stones has advantages of high stone clearance rate, reduced risk of complications, and high safety in clinical application.

Holmium laser intervention

Minimally invasive percutaneous nephrolithotomy

Serum LncRNA TapSAKI monocyte chemotactic protein-1

Interleukin-6

Prognosis

Kidney stone is a common urinary system disease in clinic. Its pathogenesis is the accumulation of crystalline substances in the patient's body, resulting in different degrees of pain in the patient's waist [1]. Relevant studies have shown that the incidence rate of complex kidney stone disease has increased significantly in China. This has brought a serious negative impact on the quality of life and healthy life of patients [2]. In view of the complexity of traditional open kidney stone surgery, holmium laser assisted minimally invasive percutaneous nephrolithotomy (mPCNL) has become a new scheme for the treatment of kidney stones with the improvement of clinical medical technology and the popularization of minimally invasive concept. Above technique has greatly improved the success rate of minimally invasive treatment of urinary calculi, and has great advantages over traditional open surgery. However, in clinical application, it will also bring some harm to patients. Whether it is traditional surgery or emerging surgery, the risk of postoperative complications still exists [3, 4]. In recent years, some scholars have found that the occurrence of kidney stones may be closely related to the disorder of Long non coding RNA (LncRNA) and inflammatory response [5]. LncRNA TapSAKI is upregulated in patients with severe acute renal injury, and its level change can be used as a prognostic indicator for patients [6]. In addition, the crystallization of kidney stones can cause pathological changes of renal tubular epithelial cells and produce a large number of inflammatory factors. This will lead to injury and inflammatory reaction of renal tubular epithelium. Among them, the level of inflammatory factors contributes to the diagnosis and evaluation of kidney stones to a certain extent [7]. However, the relationship between the expression level of LncRNA TapSAKI in serum of patients with renal calculi and inflammatory factors and prognosis of patients undergoing percutaneous nephrolithotripsy has not been reported.

In this study, the efficacy of holmium laser intervention mPCNL for patients with complicated kidney stones is explored and analyzed, and the difference of serum LncRNA TapSAKI, MCP-1 and IL-6 levels in patients with different prognosis is observed. In addition, the relationship between serum LncRNA TapSAKI and inflammatory factors MCP-1 and IL-6 is analyzed.

This paper is organized as follows: Section 2 introduces the related work, and Section 3 presents the general Information and methods. In Section 4, the results and analysis are discussed. Finally, some concluding remarks are made in Section 5.

Clinical studies have shown that the composition, diameter range, shape and location of stones in patients with complex kidney stones have certain particularity. In addition, the occurrence of this disease is often accompanied by adverse symptoms such as urinary tract infection. Therefore, the optimal surgical intervention scheme for these patients remains controversial [9]. Complex kidney stones are usually large stones with long local retention time. Some patients may develop urinary tract obstruction, leading to pain, hydronephrosis and other related complications. It may even further develop into uremia, which is life-threatening in severe cases [10]. In the past, open nephrotomy was often used in clinical practice. It requires blocking the renal pedicle vessels and cutting the renal parenchyma. For patients, it will lead to huge intraoperative trauma and may cause a certain degree of renal injury [11]. Therefore, seeking a safe and effective surgical treatment to achieve the clinical cure of complex kidney stones has been a hot issue in urology.

The mPCNL operation with holmium laser intervention mainly involves the establishment of surgical channels between the patient's skin and renal collecting system, and the endoscopic placement of calyceum, renal pelvis and ureter. At the same time, the holmium laser is used to release high energy on calculi, causing thermochemical reaction and local water vaporization effect to break the calculi into powder [12]. It is believed that mPCNL combined with holmium laser lithotripsy can simultaneously treat the stenosis of the ureteropelopeloureter junction, ureteral polyps and other soft tissue lesions, avoiding the pain of the second operation [13]. Compared with open nephrolithotomy, mPCNL with holmium laser intervention can significantly shorten the operative time and hospital stay, reduce intraoperative blood loss, and have a higher stone clearance rate. This is mainly because holmium laser interventional treatment of mPCNL has small trauma and rapid postoperative recovery. Also, it should be related to the fact that the stones were crushed thoroughly, the residual was less, and the renal colic was relieved significantly during the stone removal process. For the complexity of kidney stones, there still exists certain risk of complications of mPCNL holmium laser mPCNL under the intervention a significantly lower incidence of postoperative complications of total cut open renal nephrolithotomy. As a high-energy pulsed solid-state laser, holmium laser has the following characteristics: oscillating impact, low retreat rate, little thermal damage to surrounding tissues, and less congestion and edema of ureteral mucosa. Also, it has a certain function of intraoperative hemostasis, which helps reduce intraoperative and postoperative blood loss and postoperative complications [14]. Thus, the selection of reasonable puncture points and the establishment of ideal working channels are the key links of mPCNL holmium laser lithotripsy for stone removal and residue reduction. For small caliceal calculi that cannot be touched by percutaneous nephroscopy, the caliceal opening can be properly split with holmium laser to allow the dilated sheath to enter the caliceal for lithotripsy, thus reducing the surgical passage and postoperative complications.

It should be noted that there is no index for early prediction of kidney stones in clinical practice, and the diagnosis is usually made after the occurrence of clinical symptoms. Therefore, it is of positive significance to find effective biomarkers for early diagnosis, treatment and prognosis assessment of kidney stones. LncRNA is a class of RNA molecules with a length of more than 200 nucleotides widely existing in blood, which can regulate protein expression in the body and play an important role in regulating various physiological and pathological processes such as cell growth, apoptosis, ontogeny, signal transduction, oxidative stress and inflammatory response [15]. Some research has shown that LncRNA HOTAIR is highly expressed in acute kidney injury caused by sepsis, which can regulate miR-34A level and regulate renal tissue apoptosis, and play a certain regulatory role in renal injury caused by sepsis. Abnormal expression of LncRNA is closely related to renal injury diseases [16]. Timely detection of serum LncRNA TapSAKI, MCP-1 and IL-6 levels has certain reference value for diagnosis, treatment and prognosis assessment of kidney stones. MCP-1 is an inflammatory protein that plays an important role in the formation of calculi. It can cause the inflammatory response of renal tubular epithelial cells and produce inflammatory factors that play a promoting role. MCP-1 is involved in and affects the process of renal fibrosis [17]. Il-6 is a key factor in initiating inflammatory response, which can cause damage to renal tubular cells and capillaries, resulting in lack of nutrition and oxygen in renal tubular epithelial cells, and further promoting degeneration and necrosis of renal tubular epithelial cells [18]. It can be found positive correlation between serum LncRNA TapSAKI and THE levels of MCP-1 and IL-6 in patients with complicated kidney stones, suggesting that LncRNA TapSAKI may interact with MCP-1 and IL-6 to play a certain role in the occurrence and development of kidney stones. These results suggest that dynamic monitoring of LncRNA TapSAKI, MCP-1 and IL-6 levels is helpful for early diagnosis and prediction of renal stone disease progression.

3.1 General information

A total of 116 patients with complicated kidney stones who received surgical intervention in the urology Department of our hospital from June 2020 to June 2021 are selected and divided into two groups according to different surgical intervention methods: holmium laser combined with mPCNL group and open nephrolithotomy group, with 58 patients in each group. The holmium laser combined with mPCNL group included 32 male patients and 26 female patients, aged 30–65 years, with an average of (46.88 ± 9.99) years, and the diameter of kidney stones ranged from 2.30cm to 4.50cm, with an average of (3.34 ± 0.69)cm. The types of calculi include: staghorn calculi in 17 cases, multiple calculi in 21 cases, isolated calculi in 9 cases, horseshoe renal calculi in 4 cases, repeated renal pelvis calculi in 5 cases, caliceal diverticulum calculi in 2 cases. The open nephrotomy group included 34 male patients and 24 female patients, aged 28–66 years, with a mean of (45.59 ± 11.15) years. The diameter of kidney stones ranged from 2.40cm to 4.50cm, with a mean of (3.42 ± 0.62)cm. According to the types of stones, there were 16 staghorn shaped stones, 20 multiple stones, 8 isolated stones, 6 horseshoe shaped kidney stones, 5 repetitive renal pelvic stones, and 3 cup-shaped diverticulum stones. There are no significant statistical differences in baseline data such as gender, age, stone diameter and stone type(all P > 0.05), which confirmed that the comparison between groups is scientific and reasonable.

Inclusion criteria are as follows: (1) all patients are diagnosed by X-ray and ultrasound, and the diagnostic results are in line with the diagnostic criteria of kidney stones in the guidelines for the diagnosis and treatment of urinary calculi; (2) The clinical data of the patients are complete; (3) The patient had no history of mental illness and no signs of consciousness disorder. (4) Patients with high clinical compliance can cooperate with this study to complete relevant investigation until the end of the study.

Exclusion criteria are as follows: (1) Patients with other renal diseases, including liver and kidney dysfunction, moderate renal tubules and hydronephrosis. (2) Patients with hyperthyroidism, coagulation dysfunction, systemic immune dysfunction and other diseases; (3) Patients with infectious diseases; (4) The patient had taken steroids and other drugs affecting the inflammatory process or anticoagulant drugs in the 3 months before admission to our hospital for treatment.

3.2 Methods

3.2.1 Surgical intervention methods

Holmium laser combined with mPCNL surgical intervention is applied in the holmium laser combined with mPCNL surgical intervention group. The specific instruments included: Holmium laser lithotripter (60W), Philips M2410B color ultrasonic diagnostic instrument, color ultrasonic diagnostic instrument parameters, color ultrasonic probe frequency of 5 MHz, Renal fascial expander (F8, F10, F12, F14, F16, F18, F20), guide wire (F3.2), renal puncture needle (Coock), double J tube and F9 Olypus ureteroscopy. Specific steps: All patients in the group received general anesthesia. After successful stone resection, reverse intubation is performed to the renal pelvis after stone location is confirmed. Color ultrasound probe is used to carefully detect the lower margin of the patient's lumbar twelve ribs, and the patient's kidney is clearly identified. At the same time, reverse intubation is performed and 0.9% normal saline is injected into the body as artificial hydronephrosis. Under the guidance of color ultrasound, the renal puncture needle is used to Pierce the renal pelvis through the skin and the urine is found when the puncture needle is pulled out. Remove the needle after placing the guide wire in the renal needle sheath. The puncture scale is recorded and used as the pre-depth of renal fascia dilation. F8, F10, F12, F14, F16 and F18 renal fascia dilators are used to expand the outer sheath and indent the F20 renal fascia dilator to successfully establish the percutaneous renal channel. Olypus ureteroscopy is placed in percutaneous renal channels, connecting the monitoring system to the perfusion system. The holmium laser fiber is used to approach the calculi through ureteroscopy. The power of the holmium laser lithotripter is adjusted to 40 ~ 60W, and the calculi are crushed completely and ished out of the body along the percutaneous renal channel. Under ureteroscopy, the renal pelvis, calyx and ureter are observed for residual stones. The guide wire is inserted into the ureter, and the double J tube is inserted into the ureter along the direction of the guide wire, which is successfully passed into the bladder and fixed in the renal pelvis. The ureteroscope, renal fascial dilator and dilating sheath are removed, the skin is sutured locally, and the dressing is used. Nephrostomy tube and double J tube are routinely indwelled after lithotripsy, and abdominal plain film and abdominal color doppler ultrasound are re-examined within 2 days after surgery. If there are no large residual stones, renal fistula extraction is considered within 5 days. Otherwise, mPCNL surgery or Extracorporeal Shock Wave Lithotripsia (ESWL) should be performed at an appropriate time. If no obvious abnormality is found one month later, the double J tubes can be removed.

The open renal lithotomy group is treated with open surgical intervention. After general anesthesia, the patient is placed in the lateral decubial position with a pillow on the lower side of the waist to fully level the operative side of the waist. The 11th or 12th intercostal oblique incision is made to expose the Gerota fascia. The upper ureter, kidney and renal pelvis are routinely dissociated. For difficult impacted stones, the operation should be gradually along the direction of the incision of the renal pelvis and renal sinus until the stone is removed. Large staghorn calculi with renal parenchyma incision were removed, and the renal vessels were completely free. 250ml 20% mannitol, 40ml 10% glucose injection and 2G creatinine were injected intravenously to block the renal pedicle. Secondly, put the calyx stone forceps and take out the stones. After the renal pelvis is completely filled, the renal parenchyma is sutured intermittently. After the hemostasis is complete, the renal pelvis to the bladder is inserted into the double J tube, the renal pelvis is sutured intermittently, and the parapelvic indwelling catheter and double cavity drainage tube are placed.

3.2.2 Detection method of serum indicators

In this study, 5mL of early morning fasting venous blood is collected from all patients on the second day after admission and placed in the collection vessel. Centrifuge is used for centrifugation, with the parameters set at 3000r/min and the centrifugation radius of 10cm for 15 min. After the operation, supernatant is taken and subpacked into 1.5mL EP tube. After sealing, the serum LncRNA TapSAKI, McP-1 and IL-6 are stored in a refrigerator at -80℃ for detection. Qrt-pcr method is used to detect the expression level of LncRNA TapSAKI in serum. After serum samples are taken out, they are placed on ice in a sterile environment, and total RNA of serum samples is extracted by TRIzol. For details, refer to the instructions and precautions of TRIzol reagent. The concentration, purity and integrity of extracted RNA are detected by uv spectrophotometer. According to the instructions and precautions of the QuantiTect Reverse Transcription kit, RNA is reversely transcribed into cDNA. The cDNA is amplified according to the Perfectstart Taqman qPCR Master Mix kit operation procedure and detected by PCR. LncRNA TapSAKI used GAPDH as internal reference, and its corresponding primer sequence is shown in Table 1. The relative expression of LncRNA TapSAKI is calculated by 2^−△△CT method.

Table 1

Primer sequences of LncRNA TapSAKI and internal reference GAPDH.
The name	Forward primer	Reverse primer
LncRNA TapSAKI	5’-GCCTGGTCAAAGTCATC-3’	5’-TAACATAGGTCTCGCTCTGCTC-3’
GRAPH	5’GTGGGGCGCCCCAGGCACCA-3’	5’-CTCCTTAATGTCACGCACGATTTC-3’

Serum MCP-1 and IL-6 indicators are detected by enzyme-linked immunosorbent assay (ELISA). For specific operation steps, refer to the instructions of the corresponding kit to complete relevant operations strictly.

3.3 Observation indicators

Observation indicators include as follows: (1) Comparison of surgical indicators; (2) The stone clearance rate is compared; (3) The incidence of complications is compared; (4) Serum LncRNA TapSAKI, MCP-1 and IL-6 levels of patients with different prognosis are compared; (5) The correlation between serum LncRNA TapSAKI and MCP-1 and IL-6 in patients with kidney stones is analyzed.

3.4 Statistical Processing

All data involved in this study are processed and analyzed by SPSS 26.0 software. Mean ± standard deviation of measurement data conforming to normal distribution is expressed, and t-test is used for comparison. The count data are represented by example (%), and the comparison is performed by χ2 test. Pearson correlation analysis is used to analyze the relationship between serum LncRNA TapSAKI and MCP-1 and IL-6 in patients with complicated kidney stones, and P < 0.05 proved to be statistically significant.

4.1 Comparison of surgical indicators

The operative time and hospital stay of the holmium laser combined with mPCNL group decreased significantly than the open nephrolithotomy group. The comparison of intraoperative blood loss between groups showed that the holmium laser combined with mPCNL group had less blood loss (all P < 0.05), as shown in Table 2.

Table 2

Comparison of surgical indicators.
Group	The operation time(min)	Intraoperative blood loss(mL)	The length of time(d)
Holmium laser combined with mPCNL group(n = 58)	96.34 ± 8.40	126.43 ± 18.47	6.52 ± 1.17
Open nephrotomy and lithotomy group(n = 58)	124.72 ± 9.45	193.31 ± 15.01	14.36 ± 2.41
t	-17.094	-21.401	-22.287
P	＜0.001	＜0.001	＜0.001

4.2 Calculus clearance rate

The renal stone clearance rate in the holmium laser combined with mPCNL group is 91.38%(53/58), increased significantly than that in the open nephrotomy group (75.83%, 44/58), and the difference is statistically significant (χ2 = 5.098, P = 0.024).

4.3 Incidence of complications

The total incidence of short-term complications in the holmium laser combined with mPCNL group decreased significantly than the open nephrotomy group (all P < 0.05), as shown in Table 3.

Table 3

Comparison of postoperative complications(n,%).
Group	Bleeding	Infection of incision	Sepsis	Urinary fistula	Renal colic	The total incidence
Holmium laser combined with mPCNL group(n = 58)	1(1.72)	3(5.17)	0(0.00)	2(3.45)	4(6.90)	10(17.24)
Open nephrotomy and lithotomy group(n = 58)	3(5.17)	6(10.34)	1(1.72)	5(8.62)	7(12.07)	22(37.93)
χ2	-	-	-	-	-	6.214
P	-	-	-	-	-	0.013

4.4 Serum LncRNA TapSAKI, MCP-1 and IL-6 levels of patients with different prognosis

According to the occurrence of postoperative complications in all patients in this study as adverse prognostic events, the patients with postoperative complications are included in the poor prognosis group (n = 33), and the patients without postoperative complications are included in the good prognosis group (n = 84). Serum LncRNA TapSAKI, MCP-1 and IL-6 levels in the group with better prognosis decreased significantly than the group with poor prognosis (all P < 0.05), as shown in Table 4.

Table 4

Comparison of serum LncRNA TapSAKI, MCP-1 and IL-6 levels in patients with different prognosis.
Group	LncRNA TapSAKI	MCP-1(pg/mL)	IL-6(pg/mL)
Group with better prognosis(n = 84)	1.55 ± 0.23	134.07 ± 15.14	29.79 ± 3.31
Poor prognosis group(n = 33)	2.00 ± 0.33	184.37 ± 24.11	53.49 ± 5.47
t	-8.370	-13.535	-28.632
P	＜0.001	＜0.001	＜0.001

4.5 Analysis of the correlation between serum LncRNA TapSAKI and MCP-1 and IL-6 in patients with complicated kidney stones

Pearson correlation coefficient analysis showed that serum LncRNA TapSAKI is significantly positively correlated with MCP-1 and IL-6 indexes in patients with complicated kidney stones (all P < 0.05), as shown in Fig. 1 and Fig. 2.

In this study, the therapeutic effect of holmium laser intervention on patients with complicated kidney stones and the relationship between serum LncRNA TapSAKI, MCP-1,IL-6 and prognosis of patients is analyzed. To explore the clinical efficacy of holmium laser interventional Minimally Invasive Percutaneous Nephrolithotomy (mPCNL) for patients with complicated kidney stones is investigated, a total of 116 patients with complicated kidney stones admitted to the Department of Urology of our hospital from June 2020 to June 2021 for surgical intervention are examined. The experimental results demonstrate that mPCNL with holmium laser intervention can effectively shorten the operation time, reduce body injury, reduce complications and improve stone clearance rate for patients with complicated kidney stones. LncRNA TapSAKI may interact with MCP-1 and IL-6 to affect the occurrence and development of kidney stones. LncRNA TapSAKI, MCP-1, IL-6 have certain value for prognosis assessment. In the future, we will expand the sample size to improve the scientific degree and accuracy of the study.

Ethics approval and consent to participate

All methods were carried out in accordance with relevant guidelines and regulations. The study was approved by the Wenzhou Central Hospital’s ethics committee.

Ethics approval and consent to participate section of our manuscript.

All the experiments, including any relevant details were approved by Wenzhou Central Hospital. We confirmed that informed consent was obtained from all subjects and/or their legal guardian(s).

Consent to publish

Not applicable.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

Not applicable.

Acknowledgement

None.

Authors Contribution

Daya Wang contributed to the conception of the study, Zhijia Li performed the experiment, Jianmin Chen performed the data analyses, Ximeng Chen revised and completed the manuscript. All authors read and approved the fnal manuscript.

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No competing interests reported.

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Analysis of the therapeutic effect of holmium laser intervention on patients with complicated kidney stones and the relationship between serum LncRNA TapSAKI, MCP-1,IL-6 and prognosis of patients

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Abstract

Figures

1. Background

2. Related Work

3. General Information And Methods

3.1 General information

3.2 Methods

3.2.1 Surgical intervention methods

3.2.2 Detection method of serum indicators

3.3 Observation indicators

3.4 Statistical Processing

4. Results And Analysis

4.1 Comparison of surgical indicators

4.2 Calculus clearance rate

4.3 Incidence of complications

4.4 Serum LncRNA TapSAKI, MCP-1 and IL-6 levels of patients with different prognosis

4.5 Analysis of the correlation between serum LncRNA TapSAKI and MCP-1 and IL-6 in patients with complicated kidney stones

5. Conclusions

Declarations

References

Additional Declarations

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