Optimizing the lithotripsy timing after drainage of the upper urinary tract in patients with urolithiasis and obstructive uropathy

Introduction

The occurrence rate of urolithiasis tends to increase worldwide and the prevalence can vary depending on the regional peculiarities, race, volume of consumed water, metabolic disorders, and other concomitant diseases. Obstructive uropathy (OU) associated with stones in the urinary excretion system becomes one of the leading causes of chronic kidney disease (CKD) [1][2]. It was shown that an obstruction that duration for more than 7 days and the development of acute renal injury before the obstruction resolution were associated with a decrease in glomerular filtration rate (GFR) in the remote period [3].

Upper urinary tract (UUT) drainage is indicated when obstruction causes infection, functional impairment of the obstructed kidney, or expressed pain syndrome. It was shown that untimely resolution of obstruction in patients with the infectious process can lead to such serious complications as sepsis, pyonephrosis, and even death [4].

Decompression can be performed with a retrograde or antegrade technique. The most common methods include percutaneous nephrostomy (PCN) or installation of internal drainage stent [5]. Both methods have their advantages and disadvantages in terms of complications development, costs, quality of life, and duration of treatment. The European Association of Urology (EAU) guidelines recommend PCN and installation of a retrograde drainage stent for adequate decompression. However, the final decision is based on the capacities and equipment of a certain urological department [6]. It should be mentioned that there are no precise recommendations on the methods of draining. The analysis of recent publications showed that the optimal method for decompression of the upper urinary tract was not determined. The installation of nephrostomy drainage, as well as retrograde stenting, have high efficiency (99–100% and 80–100%, respectively) [7]. Still, the majority of authors prefer puncture-based methods of drainage for patients with infectious complications. Along with that, the timing of kidney drainage remains an acute issue as well as the main stage of surgical treatment [8]. Non-obstructive urolithiasis is often associated with recurrent urinary tract infections (UTI), so the removal of stones in such patients indicated for the prevention of UTI was effective in 89.1% of cases [9].

The microbial spectrum affects the composition of a stone. For example, urease-producing bacteria contribute to the formation of infectious stones that consist of monoammonium urate, struvite (magnesium ammonium phosphate), and/or apatite-carbonate [10], which complicates pathogenetic treatment for urolithiasis without entire elimination of uropathogen. As a rule, the most widespread infectious agents that cause UTI are gram-negative bacteria. The most common among them are E. coli [11][12].

The study aimed to optimize the timing of lithotripsy after drainage of the upper urinary tract in patients with urolithiasis and obstructive uropathy.

Materials and Methods

A total of 120 patients with urolithiasis were included in the study. The average age of patients was 46.3 ± 8.3 years old. There were 90 patients with stones in the ureteropelvic junction (UPJ) that caused UUT obstruction and 30 patients with a stone in the calyces that did not cause UUT obstruction (group of comparison). There were 54 (60%) women and 36 (40%) men in the group with obstruction and 19 (63.3%) women and 11 (36.7%) men in the group without obstruction. Patients included in the study were hospitalized as planned to the Mirotvortsev Clinical Hospital of Razumovsky Saratov State Medical University from 2018 to 2021. Patients with OU caused by a stone in UPJ underwent UUT drainage by the installation of PCN as the first step of treatment. Further, patients underwent percutaneous nephrolithotripsy (PNLT) at different times after the draining.

The criteria of inclusion were age >18 and <60 years old, presence of one stone in UPJ sized from 1 to 2 cm with density >1000 Hu, renal excretory function impairment on the side of obstruction (calyx size > 2 cm), decrease in GFR <60 ml/min calculated by the formula CKD-EPI, and informed consent.

The criteria of exclusion were congenital hydronephrosis, ureter stricture, and purulent pyelonephritis.

The authors measured the levels of the inflammation marker (IL-8) and profibrotic factor (MCP-1) in the urine to evaluate the expression of inflammatory and profibrotic alterations in the renal parenchyma. The calculated concentrations of the urine biomarkers were related to the levels of creatinine in the urine. Urine samples for the study were collected during draining and after the installation of the nephrostomy drainage directly from the nephrostomy on day 7 and once every 7 days until the surgery. To assess the process of kidney remodeling, the authors calculated the K coefficient by the patented formula (Patent RF №2735812 dated 09.11.2020) [13]:

*Kri – remodeling index

To determine the bacterial spectrum of the urine, the authors collected urine samples for cultivation and test of sensitivity to antibiotics.

Statistical analysis. Statistical data processing was performed using Statistica 10.0 (StatSoft Inc., Tusla, CA, USA) and IBM SPSS Statistics 17 (SPSS Inc., Chicago, IL, USA) software. The quantitative comparison of two independent samplings was made using Mann-Whitney U-test. The qualitative comparison of three and more independent samplings was made using Kruskal-Wallis variance analysis. The diagnostic precision of the biomarkers was evaluated using ROC analysis.

Results

The obtained results on the recalculation of the studied markers for the adjusted level of creatinine excretion in 1 ml of the urine are presented in Table 1.

ROC-curves were made for the evaluation of the sensitivity and specificity of the studied markers (Fig. 1).

The levels of diagnostically significant urinary biomarkers adjusted for the levels of excreted creatinine in patients with urolithiasis complicated by UO are presented in Table 2.

Out of 90 patients with UO included in the study, bacterial flora in the urine was detected in 55 (61%) patients. The most common bacteria included Escherichia coli 35 (63%), Proteus mirabilis – 10 (18%), Enterococcus faecalis – 8 (14.5%), Streptococcus haemolyticus – 2 (2.5%).

During the calculation of the K coefficient, the following data were obtained (Fig. 2).

By day 21, K ≤ 1.85 was observed in 11 patients with UO (12.2%) and K ˃ 1.85 – in 79 (87.8%). By day 28, K ≤ 1.85 was registered in 70 patients (88.6%). By day 35, it was revealed in 4 patients.

Cultivation of urine samples from nephrostomy drainage on days 7, 14, and 21 showed that due to antibacterial therapy, the infectious titer of the urine decreased by day 21.

Surgical treatment included PNLT performed on day 21 to patients with K ≤ 1.85 (11 patients). There were no complications after the surgery. On day 28, PNLT was performed in patients with K ≤ 1.85 (70 patients). There was no exacerbation of pyelonephritis and CKD development. On day 28, 6 patients with K ˃ 1.85 underwent PNLT. In the postoperative period, 100% of patients had exacerbation of calculous pyelonephritis and 50% of patients had a decrease in GFR within 3 months after the surgery.

On day 35, surgical treatment was performed in 4 patients with K ≤ 1.85 and one patient with К ˃ 1.85. In 1 patient with increased K levels, an attack of pyelonephritis and CKD developed in the postoperative period. Thus, lithotripsy in patients with K ˃ 1.85 led to the development of complications in 100% of cases.

Discussion

Apart from subjective symptoms that worsen the quality of patients' life, urolithiasis is associated with social-economic losses in different aspects because it often requires invasive therapy and hospitalization of the economically active population. Besides, when UO associated with urolithiasis causes such additional complications as an attack of calculous pyelonephritis or development of acute kidney injury, the social-economic burden increases because of long-term hospitalization and CKD progression [14][15][16][17]. The incidence rate of acute kidney injury caused by urolithiasis varies from 0.72% to 9.70% [18]. The resolution of obstruction has an important effect on the disease prognosis and prevents the development of pyelonephritis attacks and renal function impairment. According to Lu et al, in the Asian-Pacific Region, E. coli, K. pneumoniae, and P. aeruginosa were the most widespread species of pathogens detected in patients with UTI [19]. The study by Yongzhi et al showed that the most common microorganisms isolated from the urine samples were gram-negative followed by gram-positive bacteria and fungi. The most common pathogens among gram-negative species were E. coli, P. aeruginosa, K. pneumonia, and P. mirabilis [20]. A similar picture was observed in the present study. It was established that seven patients with complications had positive bacteriological urine cultivation tests. Besides, the present study showed that all patients with positive bacteriological cultivation tests had higher K values. At the same time, all patients received antibacterial therapy. Thus, it can be concluded that the presence of a bacterial agent is associated with higher values of remodeling index K.

Conclusion

The application of the proposed remodeling index allows the specialists to optimize the time of surgical treatment minimizing the risks of complications in the postoperative period. The presence of a bacterial agent in the urine is associated with a long-term process of remodeling of the renal parenchyma.