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Transl Androl Urol 2021 | http://dx.doi.org/10.21037/tau-20-1521
© Translational Andrology and Urology. All rights reserved.
Original Article
Changes of renal function after retrograde intrarenal surgery
using flexible ureteroscope in renal stone patients
Yu Liu1#, Zhongyu Jian1,2#, Yucheng Ma1, Yuntian Chen3, Xi Jin1, Liang Zhou1, Kunjie Wang1, Hong Li1
1Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu,
China; 2West China Biomedical Big Data Center, Sichuan University, Chengdu, China; 3Department of Radiology, West China Hospital, Sichuan
University, Chengdu, China
Contributions: (I) Conception and design: Y Liu, Z Jian, L Zhou, K Wang; (II) Administrative support: X Jin, L Zhou, K Wang, H Li; (III) Provision
of study materials or patients: Y Ma, Y Chen; (IV) Collection and assembly of data: Y Liu, Y Ma; (V) Data analysis and interpretation: Y Liu, Z Jian,
Y Ma, L Zhou; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.
#These authors are co-rst authors.
Correspondence to: Kunjie Wang; Liang Zhou. Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China
Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu 610041, China. Email: wangkj@scu.edu.cn; 694098320@qq.com.
Background: Retrograde intrarenal surgery (RIRS) is widely performed for renal stones. Theoretically,
removing renal stones could prevent the deterioration of renal function. However, two studies reported that
not all patients would see an increase in renal function after RIRS. The aim of our study was to evaluate the
change of renal function of the operative site, and to identify predictors of improvement or deterioration of
renal function after RIRS.
Methods: We retrospectively reviewed renal stones patients who received RIRS and single-photon emission
computed tomography (SPECT) before and after surgery. Improved renal function was dened as the change
of glomerular filtration rate (GFR) >10% postoperatively, and that <−10% was regarded as deteriorated
renal function. Logistic and least absolute shrinkage and selection operator regression analyses were used to
identify predictors for the improvement or deterioration of renal function, and predictive nomogram models
were built.
Results: A total of 120 renal stone patients were included. Twenty-one (17.5%), 79 (65.8%) and 20 (16.7%)
patients had improved, stable and deteriorated renal function of operative site after surgery, respectively.
Lower alkaline phosphatase, lower low-density lipoprotein, lower GFR of the operative site, thicker renal
parenchyma, higher serum creatinine, and extracorporeal shock wave lithotripsy (SWL) history were
associated with the improved renal function. The predictive accuracy of the model for the improved renal
function was 0.800. Additionally, older age, longer exible ureteroscopic time, thinner renal parenchyma and
existence of ureteral stones were risk factors for deteriorated renal function. The predictive accuracy of the
model for the deteriorated renal function was 0.725.
Conclusions: The renal function of most renal stone patients did not decrease after RIRS. For patients
with potential deterioration of renal function postoperatively, urologists could shorten exible ureteroscopic
time to prevent the occurrence of this outcome.
Keywords: Renal stones; renal function; retrograde intrarenal surgery (RIRS); predictor; nomogram model
Submitted Dec 25, 2020. Accepted for publication Apr 06, 2021.
doi: 10.21037/tau-20-1521
View this article at: http://dx.doi.org/10.21037/tau-20-1521
12
2Liu et al. Renal function after RIRS
Transl Androl Urol 2021 | http://dx.doi.org/10.21037/tau-20-1521
© Translational Andrology and Urology. All rights reserved.
Introduction
The incidence of renal stones increased rapidly worldwide
and its prevalence was about 1–19% across the world
during the past twenty years (1,2). The cost of renal stones
was about $3.79 billion in 2007 in the USA, and it would
increase to $4.57 billion in 2030 (3). The recurrence of renal
stones occurred in about half of patients five years after
lithotripsy (2). Shock wave lithotripsy (SWL), percutaneous
nephrolithotomy (PCNL) and retrograde intrarenal surgery
(RIRS) are commonly used for removing renal stones. RIRS
using flexible ureteroscope was recommended as the first
choice for patients with renal stones <2 cm (4,5). RIRS was
safe that a minority of patients had complications, including
postoperative fever (8.5%), ureteral perforation (3.5%) and
urinary tract infection (2.4%) (6).
Theoretically, removing renal stones could prevent
the deterioration of renal function. However, two studies,
evaluating the change of renal function after RIRS,
reported that not all patients would see an increase in renal
function after RIRS (7,8), which may be associated with
many factors, like preoperative renal function and exible
ureteroscopic time. In addition, both of them had some
limitations. A study used estimated glomerular filtration
rate (eGFR), which may not reect the realistic change of
renal function of operative site after RIRS (8). Based on
this, another study used single-photon emission computed
tomography (SPECT) to evaluating separate renal function
and identified factors associated with improvement
and deterioration of renal function (7). However, these
predictors were inconvenient for clinical use. Besides, this
study included renal stone patients receiving PCNL or
RIRS, whose impacts on renal function were not the same.
At present, there is limited knowledge about the effect of
RIRS on renal function of operative site. If urologists could
predict the change of renal function preoperatively, they
could pay more attention on the related risk factors and
prevent the deterioration of renal function as far as possible.
The aim of this retrospective study was to evaluate the
change of renal function after RIRS using SPECT in renal
stone patients, identify predictors and develop nomogram
model for predicting the improvement and deterioration
of renal function. We present the following article in
accordance with the STROBE reporting checklist (available
at http://dx.doi.org/10.21037/tau-20-1521).
Methods
Study design and patients
We retrospectively reviewed renal stone patients who
underwent RIRS using flexible ureteroscope in West
China Hospital, Sichuan University from July 2017 to June
2019. Renal stones were diagnosed by ultrasound of the
urinary system or abdominal computed tomography. All
these patients had unilateral stones. Patients who received
SPECT before and after surgery were included in the
study. The study was conducted in accordance with the
Declaration of Helsinki (as revised in 2013). The study was
approved by the West China Hospital of Sichuan University
Medical Research Ethics Committee approved the study
(2020508) and individual consent for this retrospective
analysis was waived.
RIRS procedures
All the surgeries were performed by one experienced
surgeon. A 4.7 Fr double J ureteral catheter was placed two
weeks before surgeries. With the patient in the lithotomic
position, a 14/16 Fr ureteral access sheath was inserted into
the ureter through a guidewire. Normal saline was irrigated
at 160 cmH2O and 0.1 L/min by pressure pumps. Stones
were fragmented using a 200 μm laser ber with holmium
laser. Pulse energy and frequency for fragmenting stones
were 1.5 J and 20 Hz. Fragments >2 mm were extracted
using a nitinol basket. The remaining fragments was dusted
when laser was set as 0.8 J and 30 Hz. A 4.7 Fr double J
ureteral catheter was again applied at the end of the surgery,
and were removed 2–3 weeks later.
Data collection
All patients received SPECT examination 12 months after
surgeries. The primary outcome was the change of renal
function of the operative site, which was evaluated by
SPECT using 99mTc-DTPA or 99mTc-DMSA. To compare
the results of this study with that reported by Piao et al. (7),
we adopted the definition of the improvement and
deterioration of renal function. Improved renal function
was defined as glomerular filtration rate (GFR) [operative
site-contralateral site (postoperative)] – [operative site-
contralateral site (preoperative)] >10%, and that <−10%
3
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was regarded as deteriorated renal function. The remaining
patients were categorized into stable renal function group.
Preoperative factors associated with the change of renal
function included demographic characteristics, disease
history, operation data, laboratory data and imaging data.
General characteristics were age, gender, body mass index
(BMI) and history of smoking and drinking. Disease
history mainly included diabetes mellitus, hypertension,
hyperuricemia or gout and renal tubular acidosis. Operation
data included the history of nephrolithotomy and flexible
ureteroscopic time, which was defined as the time when
endoscopy was inserted into the urethra. Apart from
GFR, we also collected the following data, including
renal parenchymal thickness, existence of hydronephrosis,
ureteral stone and ureterostenosis, renal stone volume and
maximal renal stone size. These data could be measures
using IntelliSpace Discovery platform (Philips) (9). The
schematic diagram of measuring renal stone volume,
maximal renal stone size and renal parenchymal thickness
were shown in Figure 1.
Statistical analysis
Mean and standard deviation were calculated for quantitative
factors when they were symmetrically distributed, they were
presented as mean and standard deviation, and analyzed
using analysis of variance (ANOVA). Otherwise, they were
shown as median and interquartile range, and compared
by Kruskal-Wallis test. Categorical factors were presented
as quantity and percentage, and analyzed using Chi-square
test or Fisher’s Exact test. We used logistic regression
analysis and least absolute shrinkage and selection operator
(LASSO) regression analysis to nd factors associated with
the improvement and deterioration of renal function, and
two models for predicting the change of renal function
after RIRS were also built. Nomograms of models were
drawn. The sensitivity, specificity and predictive accuracy
of the models were calculated. All the statistical analyses
were conducted using R (version 3.6.3). P value <0.05 was
considered as signicantly different.
Results
Characteristics of patients and stones
A total of 120 patients were included in the study. About 21
(17.5%), 79 (65.8%) and 20 (16.7%) patients had improved,
stable and deteriorated renal function of operative site
postoperatively, respectively. The mean age was 47.4±
11.7 years, and about two-thirds of patients were males.
Half of the patients had received surgeries for removing
renal stones, including SWL, RIRS, PCNL and open
nephrolithotomy, with no significant difference between
three groups (P=0.559). Based on GFR of the operative
site, 40.0% patients had mild renal impairment, followed
by moderate renal impairment (28.3%), normal renal
function (21.7%) and severe renal impairment (10.0%), and
GFR grade was statistically different between three groups
(P=0.046). About half of the patients had ureteral stone
or ureterostenosis. The median renal stone volume was
1.80 cm3 (Table 1).
Figure 1 Segmentations of kidney on computed tomography in a renal stone patient. (A) Drawing an outline of renal stone in one
segmentation and calculating its volume. (B) Calculating the maximal renal stone size of renal stone. (C) Calculating the renal parenchymal
thickness.
A B C
4Liu et al. Renal function after RIRS
Transl Androl Urol 2021 | http://dx.doi.org/10.21037/tau-20-1521
© Translational Andrology and Urology. All rights reserved.
Table 1 Characteristics of patients and stones
Variable Total (n=120) Improved (n=21) Stable (n=79) Deteriorated (n=20) P value
Demographic characteristics
Age (year)† 47.4 (11.7) 46.9 (9.9) 46.4 (12.1) 51.5 (11.4) 0.219
Gender (male)§ 81 (67.5%) 11 (52.4%) 57 (72.2%) 13 (65.0%) 0.22
BMI (kg/m2)‡ 24.60 (3.73) 23.81 (3.22) 24.57 (4.08) 25.08 (2.86) 0.52
Smoking (yes)§ 36 (30.0%) 4 (19.0%) 24 (30.4%) 8 (40.0%) 0.34
Drinking (yes)§ 28 (23.3%) 3 (14.3%) 20 (25.3%) 5 (25.0%) 0.558
Disease history
Diabetes mellitus (yes)§ 9 (7.5%) 0 (0.0%) 7 (8.9%) 2 (10.0%) 0.351
Hypertension (yes)§ 32 (26.7%) 8 (38.5%) 17 (21.5%) 7 (35.0%) 0.204
Hyperuricemia/Gout (yes)§ 38 (31.7%) 6 (28.6%) 26 (32.9%) 6 (30.0%) 0.916
Renal tubular acidosis (yes)§ 2 (1.7%) 1 (4.8%) 0 (0.0%) 1 (5.0%) 0.141
Operation data
SWL history (yes)§ 30 (25.0%) 9 (42.9%) 15 (19.0%) 6 (30.0%) 0.069
RIRS history (yes)§ 20 (16.7%) 2 (9.5%) 13 (16.5%) 5 (25.0%) 0.412
PCNL history (yes)§ 15 (12.5%) 2 (9.5%) 12 (15.2%) 1 (5.0%) 0.423
Open nephrolithotomy history (yes)§ 12 (10.0%) 1 (4.8%) 9 (11.4%) 2 (10.0%) 0.667
nephrolithotomy history (yes)§ 60 (50.0%) 11 (52.4%) 37 (46.8%) 12 (60.0%) 0.559
Flexible ureteroscopic time (min)‡ 26.80 (24.65) 26.10 (22.45) 24.30 (24.80) 34.05 (40.90) 0.214
Laboratory data
RBC (1012/L)† 4.63 (0.54) 4.40 (0.59) 4.72 (0.54) 4.53 (0.46) 0.037
Hemoglobin (g/L)† 136.80 (17.89) 132.67 (16.87) 137.96 (18.71) 136.55 (15.63) 0.487
ALP (IU/L)† 80.79 (22.10) 70.38 (17.93) 83.92 (23.44) 79.35 (17.41) 0.041
Serum uric acid (μmol/L)† 379.11 (88.94) 367.10 (96.43) 381.75 (87.82) 381.30 (88.86) 0.795
Serum creatinine (μmol/L)‡ 83.80 (30.75) 87.00 (37.50) 83.10 (26.60) 89.90 (35.25) 0.451
LDL (mmol/L)† 2.61 (0.75) 2.27 (0.66) 2.73 (0.72) 2.47 (0.82) 0.026
Triglyceride (mmol/L)‡ 1.66 (1.30) 1.52 (2.99) 1.59 (1.27) 1.93 (1.60) 0.145
Cholesterol (mmol/L)† 4.50 (0.88) 4.37 (0.71) 4.53 (0.91) 4.51 (0.91) 0.765
HDL (mmol/L)‡ 1.14 (0.37) 1.21 (0.43) 1.14 (0.35) 1.10 (0.55) 0.532
Imaging data
GFR of operative site (mL/min)† 33.47 (14.60) 26.92 (9.96) 36.01 (14.80) 30.34 (15.71) 0.022
GFR of operative site§ 0.046
Severe renal impairment (<15 mL/min) 12 (10.0%) 2 (9.5%) 6 (7.6%) 4 (20.0%)
Moderate renal impairment (15–30 mL/min) 34 (28.3%) 10 (47.6%) 19 (24.1%) 5 (25.0%)
Mild renal impairment (30–45 mL/min) 48 (40.0%) 9 (42.9%) 31 (39.2%) 8 (40.0%)
Normal renal function (>45 mL/min) 26 (21.7%) 0 (0.0%) 23 (29.1%) 3 (15.0%)
Table 1 (continued)
5
Translational Andrology and Urology, 2021
Transl Androl Urol 2021 | http://dx.doi.org/10.21037/tau-20-1521
© Translational Andrology and Urology. All rights reserved.
Predictors for the improved renal function after RIRS and
predictive model
We firstly performed univariate logistic regression
analysis and then selected factors with P value <0.100 for
multivariate logistic regression analysis. It showed that
lower alkaline phosphatase (ALP), lower low-density
lipoprotein (LDL), lower GFR of the operative site, thicker
renal parenchymal, higher serum creatinine and SWL
history were predictors for the improved renal function of
the operative site after RIRS (P<0.050) (Table 2). Apart from
these factors, LASSO regression analysis also showed that
BMI and HDL were associated with improvement of renal
function (Figure 2A,B).
Due to the limitation of sample size, we only selected
six factors both occurred in logistic and LASSO regression
analyses to build a model for predicting the improvement
of renal function, including SWL history, ALP, GFR of
the operative site, LDL, renal parenchymal thickness
and serum creatinine. The area under the curve (AUC)
of receiver operating characteristic (ROC) was 0.798
(Figure 2C). We also performed an internal four-fold cross-
validation for 1000 times, and the mean AUC of ROC was
0.730 (95% CI, 0.728–0.732). To decrease misprediction
rate to supervise patients’ follow-up, the cut-off value of
probability of improved renal function was set as 0.256,
and the sensitivity and specificity were 0.667 and 0.828
respectively, with the predictive accuracy of 0.800. To
visualize the predictive model, a nomogram was drawn
(Figure 2D). Hodges-Lehmmann test showed that there was
no mismatch between predictive model and retrospective
cohort (χ2=8.473, P=0.389).
Predictors for the deteriorated renal function after RIRS
and predictive model
Similarly, univariate logistic regression analysis showed
that older age, larger renal stone size, longer flexible
ureteroscopic time, thinner renal parenchyma and existence
of ureteral stones were risk factors for deteriorated renal
function after RIRS (P<0.100). The last three factors
were still statistically different in multivariate logistic
regression analysis (P<0.050) (Table 3). In addition, LASSO
regression analysis screened out factors associated with the
deterioration of renal function, including age, endoscopic
time and renal parenchymal thickness (Figure 3A,B).
A predictive model for deteriorated renal function was
developed based on four factors both occurred in logistic
and LASSO regression analyses, including age, renal
parenchymal thickness, endoscopic time and ureteral stone.
The AUC of ROC was 0.807 (Figure 3C). After 1000
times cross validation, it was 0.745 (95% CI, 0.743–0.748).
When the cut-off value of probability of deteriorated renal
function was 0.162, the sensitivity (0.800) and specificity
(0.710) were high. The predictive accuracy was 0.725. The
predictive nomogram was also demonstrated (Figure 3D).
Hodges-Lehmmann test indicated that indicated that the
predictive accuracy of the nomogram model was good
(χ2=3.977, P=0.859).
Table 1 (continued)
Variable Total (n=120) Improved (n=21) Stable (n=79) Deteriorated (n=20) P value
Renal parenchymal thickness (mm)† 21.60 (5.28) 23.63 (5.63) 21.66 (5.18) 19.25 (4.51) 0.027
Hydronephrosis (yes)§ 91 (75.8%) 18 (85.7%) 59 (74.7%) 14 (70.0%) 0.461
Ureteral stone (yes)§ 45 (37.5%) 8 (38.1%) 34 (43.0%) 3 (15.0%) 0.069
Ureterostenosis (yes)§ 44 (36.7%) 7 (33.3%) 30 (38.0%) 7 (35.0%) 0.913
Ureteral stone or ureterostenosis (yes)§ 62 (51.7%) 9 (42.9%) 46 (58.2%) 7 (35.0%) 0.120
Renal stone volume (cm3)‡ 1.80 (3.46) 2.02 (3.94) 1.75 (3.14) 2.46 (4.69) 0.188
Maximal renal stone size (mm)‡ 13.7 (11.0) 10.8 (11.5) 12.8 (11.3) 15.7 (8.1) 0.162
†, data were presented as mean (standard deviation), and were analyzed with analysis of variance (ANOVA); ‡, data were presented
as median (interquartile range), and were analyzed with Kruskal-Wallis test; §, data were presented as quantity (percentage), and were
analyzed with Chi-square test or Fisher’s Exact test. BMI, body mass index; SWL, shock wave lithotripsy; RIRS, retrograde intrarenal
surgery; PCNL, percutaneous nephrolithotomy; RBC, red blood cell; ALP, alkaline phosphatase; LDL, low density lipoprotein; HDL, high
density lipoprotein; GFR, glomerular filtration rate.
6Liu et al. Renal function after RIRS
Transl Androl Urol 2021 | http://dx.doi.org/10.21037/tau-20-1521
© Translational Andrology and Urology. All rights reserved.
Table 2 Factors associated with the improved renal function of operative site after retrograde intrarenal surgery
Variable
Univariate Multivariate
OR (95% CI) P value OR (95% CI) P value
Demographic characteristics
Age (year) 1.004 (0.964–1.045) 0.857
Gender (male) 0.456 (0.175–1.190) 0.108
BMI (kg/m2) 1.118 (0.937–1.333) 0.216
Smoking (yes) 2.030 (0.631–6.526) 0.235
Drinking (yes) 2.027 (0.550–7.465) 0.288
Disease history
Diabetes mellitus (yes) 1.001 (0.376–2.665) 0.999
Hypertension (yes) 0.520 (0.193–1.404) 0.197
Hyperuricemia/Gout (yes) 1.194 (0.424–3.365) 0.737
Renal tubular acidosis (yes) 0.204 (0.012–3.401) 0.268
Operation data
SWL history (yes) 0.359 (0.133–0.966) 0.042 0.321 (0.116–0.891) 0.029
RIRS history (yes) 2.111 (0.451–9.886) 0.343
PCNL history (yes) 1.436 (0.299–6.899) 0.651
Open nephrolithotomy history (yes) 2.500 (0.305–20.495) 0.393
nephrolithotomy history (yes) 0.891 (0.347–2.287) 0.810
Flexible ureteroscopic time (min) 1.002 (0.978–1.028) 0.848
Laboratory data
RBC (1012/L) 2.602 (1.070–6.327) 0.035 2.381(0.800–7.086) 0.119
Hemoglobin (g/L) 1.015 (0.990–1.042) 0.246
ALP (IU/L) 1.032 (1.005–1.059) 0.021 1.033 (1.005–1.062) 0.019
Serum uric acid (μmol/L) 1.002 (0.997–1.007) 0.495
Serum creatinine (μmol/L) 0.985 (0.968–1.001) 0.071 0.975 (0.957–0.994) 0.011
LDL (mmol/L) 2.211 (1.103–4.429) 0.025 2.212 (1.082–4.522) 0.030
Triglyceride (mmol/L) 0.807 (0.603–1.080) 0.148
Cholesterol (mmol/L) 1.225 (0.711–2.109) 0.465
HDL (mmol/L) 0.507 (0.105–2.457) 0.399
Imaging data
GFR of operative site (mL/min) 1.042 (1.005–1.080) 0.026 1.043 (1.005–1.082) 0.026
Renal parenchymal thickness (mm) 0.909 (0.824–1.002) 0.056 0.903 (0.817–0.998) 0.049
Hydronephrosis (yes) 0.468 (0.127–1.720) 0.253
Ureteral stone (yes) 0.970 (0.368–2.559) 0.951
Ureterostenosis (yes) 1.194 (0.442–3.226) 0.727
Table 2 (continued)
7
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Table 2 (continued)
Variable
Univariate Multivariate
OR (95% CI) P value OR (95% CI) P value
Ureteral stone or ureterostenosis (yes) 1.536 (0.594–3.973) 0.376
Renal stone volume (cm3) 0.989 (0.902–1.084) 0.814
Maximal renal stone size (mm) 1.022 (0.966–1.081) 0.444
BMI, body mass index; SWL, shock wave lithotripsy; RIRS, retrograde intrarenal surgery; PCNL, percutaneous nephrolithotomy; RBC, red
blood cell; ALP, alkaline phosphatase; LDL, low density lipoprotein; HDL, high density lipoprotein; GFR, glomerular filtration rate; OR, odds
ratio; CI, confidence intervals.
Figure 2 Predictive model for predicting the improved renal function after retrograde intrarenal surgery using exible ureteroscope. (A)
LASSO coefcient proles of all the characteristics of patients and stones. (B) Identication of the optimal penalization coefcient Lambda
in the LASSO model with 10-fold cross validation via minimum criteria. (C) Receiver operating characteristic curve of predictive model. (D)
The nomogram of predictive model. LASSO, least absolute shrinkage and selection operator.
A B C
D
16 16 16 16 10 5 16 16 16 16 16 16 16 16 16 16 16 16 15 12 11 10 9 8 7 6 5 5 3
Log lambda
0 10 20 30 40 50 60 70 80 90 100
240 220 200 180 160 140 120 100 80 60 40 20
65 60 55 50 45 40 35 30 25 20 15 10 5
5 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0
10 12 14 16 18 20 22 24 26 28 30 32 34
−8 −7 −6 −5 −4 −3 −2 −1 0 1 2 3 4
20 40 60 80 100 120 140 160 180 200 220
Yes
No
Points
SWL_history
ALP
GFR_of_operative_site
LDL
Serum_creatinine
Renal_parenchymal_
thickness
Total points
Linear predictor
Probability
0 50 100 150 200 250 300 350
Log (l) Specificity
AUC: 0.798
−8 −7 −6 −5 −4 −3 −8 −7 −6 −5 −4 −3 1.0 0.8 0.6 0.4 0.2 0.0
Coefficients
Binomial deviance
Sensitivity
1
0
−1
−2
−3
1.8
1.6
1.4
1.2
1.0
0.8
1.0
0.8
0.6
0.4
0.2
0.0
0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9
8Liu et al. Renal function after RIRS
Transl Androl Urol 2021 | http://dx.doi.org/10.21037/tau-20-1521
© Translational Andrology and Urology. All rights reserved.
Table 3 Factors associated with the deteriorated renal function of operative site after retrograde intrarenal surgery
Variable
Univariate Multivariate
OR (95% CI) P value OR (95% CI) P value
Demographic characteristics
Age (year) 1.041 (0.994–1.089) 0.086 1.041 (0.995–1.090) 0.082
Gender (male) 1.144 (0.417–3.143) 0.794
BMI (kg/m2) 0.970 (0.816–1.152) 0.726
Smoking (yes) 1.714 (0.634–4.639) 0.289
Drinking (yes) 1.116 (0.366–3.400) 0.847
Disease history
Diabetes mellitus (yes) 1.476 (0.283–7.691) 0.644
Hypertension (yes) 1.615 (0.580–4.499) 0.359
Hyperuricemia/Gout (yes) 0.911 (0.320–2.588) 0.861
Renal tubular acidosis (yes) 5.211 (0.312–86.975) 0.250
Operation data
SWL history (yes) 1.357 (0.470–3.920) 0.573
RIRS history (yes) 1.889 (0.597–5.974) 0.279
PCNL history (yes) 0.323 (0.040–2.611) 0.289
Open nephrolithotomy history (yes) 1.000 (0.202–4.955) 1.000
nephrolithotomy history (yes) 1.625 (0.612–4.316) 0.330
Flexible ureteroscopic time (min) 1.031 (1.007–1.055) 0.012 1.033 (1.008–1.058) 0.008
Laboratory data
RBC (1012/L) 0.667 (0.277–1.064) 0.365
Hemoglobin (g/L) 0.999 (0.973–1.026) 0.945
ALP (IU/L) 0.996 (0.975–1.019) 0.749
Serum uric acid (μmol/L) 1.000 (0.995–1.006) 0.904
Serum creatinine (μmol/L) 1.007 (0.990–1.025) 0.412
LDL (mmol/L) 0.738 (0.382–1.425) 0.365
Triglyceride (mmol/L) 1.071 (0.814–1.409) 0.624
Cholesterol (mmol/L) 1.011 (0.583–1.753) 0.969
HDL (mmol/L) 1.747 (0.349–8.750) 0.497
Imaging data
GFR of operative site (mL/min) 0.982 (0.949–1.016) 0.293
Renal parenchymal thickness (mm) 0.902 (0.820–0.991) 0.032 0.901 (0.817–0.992) 0.035
Hydronephrosis (yes) 0.697 (0.241–2.019) 0.506
Ureteral stone (yes) 4.103 (1.130–14.907) 0.032 4.284 (1.165–15.749) 0.029
Ureterostenosis (yes) 0.917 (0.336–2.504) 0.865
Table 3 (continued)
9
Translational Andrology and Urology, 2021
Transl Androl Urol 2021 | http://dx.doi.org/10.21037/tau-20-1521
© Translational Andrology and Urology. All rights reserved.
Figure 3 Predictive model for predicting the deteriorated renal function after retrograde intrarenal surgery using exible ureteroscope. (A)
LASSO coefcient proles of all the characteristics of patients and stones. (B) Identication of the optimal penalization coefcient Lambda
in the LASSO model with 10-fold cross validation via minimum criteria. (C) Receiver operating characteristic curve of predictive model. (D)
The nomogram of predictive model. LASSO, least absolute shrinkage and selection operator.
Table 3 (continued)
Variable
Univariate Multivariate
OR (95% CI) P value OR (95% CI) P value
Ureteral stone or ureterostenosis (yes) 0.441 (0.162–1.197) 0.108
Renal stone volume (cm3) 1.038 (0.954–1.130) 0.384
Maximal renal stone size (mm) 1.047 (0.992–1.105) 0.093 1.051 (0.994–1.111) 0.083
BMI, body mass index; SWL, shock wave lithotripsy; RIRS, retrograde intrarenal surgery; PCNL, percutaneous nephrolithotomy; RBC, red
blood cell; ALP, alkaline phosphatase; LDL, low density lipoprotein; HDL, high density lipoprotein; GFR, glomerular filtration rate; OR, odds
ratio; CI, confidence intervals.
A B C
D
D
15 13 9 3 16 16 16 16 16 15 15 15 15 15 15 15 14 12 10 10 9 9 6 3 3 2 0
Log lambda
0 10 20 30 40 50 60 70 80 90 100
34 32 30 28 26 24 22 20 18 16 14 12 10
0 10 20 30 40 50 60 70 80 90 100 110 120
15 20 25 30 35 40 45 50 55 60 65 70 75 80
0 20 40 60 80 100 120 140 160 180 200 220 240 260
−5 −4.5 −4 −3.5 −3 −2.5 −2 −1.5 −1 −0.5 0 0.5 1 1.5 2
Points
Age
Endoscopic_time
Ureteral_stone
Renal_parenchymal_
thickness
Total points
Linear predictor
Probability
Log (l) Specificity
AUC: 0.807
−6 −5 −4 −3 −8 −7 −6 −5 −4 −3 1.0 0.8 0.6 0.4 0.2 0.0
Coefficients
Binomial deviance
Sensitivity
1.5
1.0
0.5
0.0
−0.5
−1.0
1.3
1.2
1.1
1.0
0.9
0.8
1.0
0.8
0.6
0.4
0.2
0.0
0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8
Yes
No
10 Liu et al. Renal function after RIRS
Transl Androl Urol 2021 | http://dx.doi.org/10.21037/tau-20-1521
© Translational Andrology and Urology. All rights reserved.
Discussion
In the study, we used SPECT to evaluated the change of
renal function after RIRS and found that the improvement
and deterioration of renal function of operative site
occurred in 17.5% and 16.7% of patients, which were
slightly different from the previous studies (7,8). Piao et al.
reported that the increase and decrease of renal function of
operative site were seen in 58.5% and 5.7% of renal stone
patients after surgery respectively (7). The examination of
separate renal function and definition of its change were
the same in this study and ours. The reason for higher
deteriorated rate and lower improved rate in our study may
be that most renal stone patients in our study had already
received nephrolithotomy previously, like SWL, PCNL and
RIRS. Another study found that the deterioration of renal
function only occurred in 4.9% patients after surgery, which
was lower than that of our study (8). This study used eGFR
to evaluate renal function. When the contralateral normal
kidney still had compensatory potency, eGFR may not
change signicantly even though renal function of operative
site decreased slightly postoperatively.
SWL history was positively correlated with the
improvement of renal function. Fayad et al. reported
that there was no statistically significant change in GFR
six months after SWL using SPECT (10). Removing
renal stones using SWL delayed the deterioration of
renal function in patients with nephrolithiasis (11). All
these evidences verified the benefits of SWL for renal
function. In addition, we found that higher ALP may
prevent the improvement of renal function. ALP, an
enzyme hydrolyzing pyrophosphate (a vascular calcication
inhibitor), could promote heterotopic calcification (12).
Thus, elevated ALP may be associated with the recurrence
of renal stones, leading to further renal deterioration. We
also found that LDL was low in patients with improved
renal function. Jiang et al. reported that high baseline
LDL was associated with a more significant decrease in
eGFR (13). The patients with LDL <2.6 mmol/L showed
less progression of chronic renal disease than those with
higher LDL (14). Interestingly, we found that thicker renal
parenchyma promoted the improvement of renal function,
while higher GFR of operative site and low serum creatinine
may prevent this process. This result was not unexpectedly,
because these kidneys with deteriorated function had space
to improve, especially when the renal morphology was not
affected. This phenomenon also occurred in the study of
Piao et al. which reported that more than half of patients
with abnormal separate renal function before surgery had
improved renal function postoperatively (7). Nordenström
et al. found that low baseline renal function was a predictor
of improvement of renal function in infants and children
after surgery for ureteropelvic junction obstruction (15).
When it comes to deterioration of renal function after
RIRS, we found that longer flexible ureteroscopy time,
existence of ureteral stones and thinner renal parenchyma
may be pivotal risk factors. Lane et al. also reported that
prolonged ureteroscopy time was associated with increased
complication rates (16). During flexible ureteroscopy,
normal saline was continuously injected into the pelvis,
which increased the intrarenal pressure. Existance of
ureteral stones prevented the urine from owing smoothly,
and the urine collected in the renal pelvis, followed by
increasing pressure. Excessive pressure leads to renal pelvis
and tubular expansion and interstitial cellular infiltration,
which induced production of inflammatory cytokines
and oxidative stress, followed by tubular cell apoptosis,
interstitial brosis, nephron loss, thinner renal parenchyma
and nal deteriorated renal function (17-19).
Compared with previous studies, we built models with
high predictive accuracy for predicting the improvement
and deterioration of renal function after RIRS. Using these
models, urologists could screene out patients whose renal
function are more likely to decrease postoperatively and
gave some suggestions on how to prevent the recurrent
renal stones, like sufcient drinking water (>2,500 mL/day),
less salt and protein intake, more fruits intake rich in citrate
and more exercise. Frequent urinary ultrasonography was
also important during the follow-up to supervise renal
stones and hydronephrosis as it was easy to perform without
any radiation. Additionally, urologists could communicate
with these patients about the renal function deterioration
after surgery to reduce potential medical disputes and
improve physician-patient relationships.
The study had several advantages and features. First,
SPECT was used to precisely measure the renal function of
operative site. Second, renal stone volume was accurately
measured using IntelliSpace Discovery platform (Philips),
which was rstly applied for studying renal stones. Third,
we developed models for predicting the change of renal
function after RIRS, which may support clinical decision-
making.
However, there were also some limitations that could
not be neglected. First, the sample size was relatively
small. Some patients did not routinely receive urinary
11
Translational Andrology and Urology, 2021
Transl Androl Urol 2021 | http://dx.doi.org/10.21037/tau-20-1521
© Translational Andrology and Urology. All rights reserved.
ultrasonography postoperatively in our hospital, which
resulted in the loss of follow-up of renal stone patients.
Second, about a third of renal stone patients were
accompanied with ureteral stones. Theoretically, ureteral
stones would induce hydronephrosis, followed by the
decrease of renal function. We should have evaluated the
change of renal function of renal stone patients with or
without ureteral stones separately. However, due to the
small sample size, there may be biases when performing this
subgroup analysis. More studies with large sample size are
needed to tackle this problem.
Conclusions
the renal function of most renal stone patients did
not decrease after RIRS. For patients with potential
deterioration of renal function postoperatively, urologists
could shorten flexible ureteroscopic time to prevent the
occurrence of this outcome.
Acknowledgments
We thank Xiaodi Zhang [Philips (China) Investment Co.,
Ltd. Chengdu Branch] for the instruction of measuring
renal stone volume.
Funding: This work was supported by the Project of
Science and Technology Department of Sichuan Province
(2018SZ0118); the Project of Sichuan Province Health
Department (ZH2017–101); and 1.3.5 project for disciplines
of excellence, West China Hospital, Sichuan University
(ZY2016104, ZYJC18015).
Footnote
Reporting Checklist: The authors have completed the
STROBE reporting checklist. Available at http://dx.doi.
org/10.21037/tau-20-1521
Data Sharing Statement: Available at http://dx.doi.
org/10.21037/tau-20-1521
Conicts of Interest: All authors have completed the ICMJE
uniform disclosure form (available at http://dx.doi.
org/10.21037/tau-20-1521). The authors have no conicts
of interest to declare.
Ethical Statement: The authors are accountable for all
aspects of the work in ensuring that questions related
to the accuracy or integrity of any part of the work are
appropriately investigated and resolved. The study was
conducted in accordance with the Declaration of Helsinki
(as revised in 2013). The study was approved by the West
China Hospital of Sichuan University Medical Research
Ethics Committee approved the study (2020508) and
individual consent for this retrospective analysis was waived.
Open Access Statement: This is an Open Access article
distributed in accordance with the Creative Commons
Attribution-NonCommercial-NoDerivs 4.0 International
License (CC BY-NC-ND 4.0), which permits the non-
commercial replication and distribution of the article with
the strict proviso that no changes or edits are made and the
original work is properly cited (including links to both the
formal publication through the relevant DOI and the license).
See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
References
1. Sorokin I, Mamoulakis C, Miyazawa K, et al.
Epidemiology of stone disease across the world. World J
Urol 2017;35:1301-20.
2. Liu Y, Chen Y, Liao B, et al. Epidemiology of urolithiasis
in Asia. Asian J Urol 2018;5:205-14.
3. Antonelli JA, Maalouf NM, Pearle MS, et al. Use of the
National Health and Nutrition Examination Survey to
calculate the impact of obesity and diabetes on cost and
prevalence of urolithiasis in 2030. Eur Urol 2014;66:724-9.
4. NICE Guideline - Renal and ureteric stones: assessment
and management: NICE (2019) Renal and ureteric stones:
assessment and management. BJU Int 2019;123:220-32.
5. Somani BK, Ploumidis A, Pappas A, et al. Pictorial review
of tips and tricks for ureteroscopy and stone treatment:
an essential guide for urologists from PETRA research
consortium. Transl Androl Urol 2019;8:S371-80.
6. Jiang H, Yu Z, Chen L. Minimally Invasive Percutaneous
Nephrolithotomy versus Retrograde Intrarenal Surgery
for Upper Urinary Stones: A Systematic Review and Meta-
Analysis. Biomed Res Int 2017;2017:2035851.
7. Piao S, Park J, Son H, et al. Evaluation of renal function
in patients with a main renal stone larger than 1 cm and
perioperative renal functional change in minimally invasive
renal stone surgery: a prospective, observational study.
World J Urol 2016;34:725-32.
8. Hoarau N, Martin F, Lebdai S, et al. Impact of retrograde
exible ureteroscopy and intracorporeal lithotripsy on
kidney functional outcomes. Int Braz J Urol 2015;41:920-6.
12 Liu et al. Renal function after RIRS
Transl Androl Urol 2021 | http://dx.doi.org/10.21037/tau-20-1521
© Translational Andrology and Urology. All rights reserved.
9. Laukamp KR, Thiele F, Shakirin G, et al. Fully automated
detection and segmentation of meningiomas using deep
learning on routine multiparametric MRI. Eur Radiol
2019;29:124-32.
10. Fayad A, El-Sheikh MG, Abdelmohsen M, et al. Evaluation
of renal function in children undergoing extracorporeal
shock wave lithotripsy. J Urol 2010;184:1111-4.
11. Yoo DE, Han SH, Oh HJ, et al. Removal of kidney stones
by extracorporeal shock wave lithotripsy is associated with
delayed progression of chronic kidney disease. Yonsei Med
J 2012;53:708-14.
12. Zhan X, Yang Y, Chen Y, et al. Serum alkaline phosphatase
levels correlate with long-term mortality solely in
peritoneal dialysis patients with residual renal function.
Ren Fail 2019;41:718-25.
13. Jiang S, Sun X, Gu H, et al. Age-related change in
kidney function, its inuencing factors, and association
with asymptomatic carotid atherosclerosis in healthy
individuals--a 5-year follow-up study. Maturitas
2012;73:230-8.
14. Ozsoy RC, van der Steeg WA, Kastelein JJ, et al.
Dyslipidaemia as predictor of progressive renal failure and
the impact of treatment with atorvastatin. Nephrol Dial
Transplant 2007;22:1578-86.
15. Nordenström J, Koutozi G, Holmdahl G, et al. Changes
in differential renal function after pyeloplasty in infants
and children. J Pediatr Urol 2020;16:329.e1-329.e8.
16. Lane J, Whitehurst L, Hameed BMZ. Correlation of
Operative Time with Outcomes of Ureteroscopy and
Stone Treatment: a Systematic Review of Literature. Curr
Urol Rep 2020;21:17.
17. Chevalier RL, Thornhill BA, Forbes MS, et al.
Mechanisms of renal injury and progression of renal
disease in congenital obstructive nephropathy. Pediatr
Nephrol 2010;25:687-97.
18. Grande MT, Pérez-Barriocanal F, López-Novoa JM. Role
of inammation in túbulo-interstitial damage associated to
obstructive nephropathy. J Inamm (Lond) 2010;7:19.
19. Wu B, Brooks JD. Gene expression changes induced
by unilateral ureteral obstruction in mice. J Urol
2012;188:1033-41.
Cite this article as: Liu Y, Jian Z, Ma Y, Chen Y, Jin X, Zhou L,
Wang K, Li H. Changes of renal function after retrograde
intrarenal surgery using flexible ureteroscope in renal stone
patients. Transl Androl Urol 2021. doi: 10.21037/tau-20-1521
