Analysis of efficacy factors in unilateral obstructive severe renal insufficiency

doi:10.21203/rs.3.rs-4146127/v1

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Analysis of efficacy factors in unilateral obstructive severe renal insufficiency

https://doi.org/10.21203/rs.3.rs-4146127/v1

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Objective

To investigate the predictors of renal function recovery after treatment of severe renal impairment in unilateral upper urinary tract obstruction (UUTO).

Methods

From January 2014 to January 2023, the clinical data of 142 patients with unilateral UUTO severe renal injury who were admitted to the First Affiliated Hospital of Chongqing Medical University were collected. The estimated glomerular filtration rate (eGFR) of patients before treatment, GFR value of ^99mTc-DTPA dynamic renal scintigraphy before treatment, C-reactive protein before treatment, and body mass index were used as independent variables, a predictive analysis of the change in GFR (GFRd) after treatment. Multiple linear regression analysis was used to predict the GFRd after treatment, and the difference was statistically significant with P < 0.05. At the same time, the categorical variables such as sex, obstruction site and normal renal function were compared with GFRd by two-sample t-test or one-way ANOVA, and the difference was statistically significant with P < 0.05.

Results

The multiple linear regression results showed that the GFR value of the affected kidney obtained by ^99mTc-DTPA dynamic renal scintigraphy and C-reactive protein were significantly correlated with the GFRd value women and patients with renal obstruction had a higher mean GFRd than men and patients with ureteral obstruction, but the difference was not statistically significant.

Conclusion

The GFR value of the affected kidney obtained by ^99mTc-DTPA dynamic renal scintigraphy and C-reactive protein before treatment are important reference indicators for evaluating the efficacy of patients with severe renal insufficiency caused by unilateral upper urinary tract obstruction. And the role of ^99mTc-DTPA dynamic renal scintigraphy was irreplaceable when unilateral renal function was impaired or it was necessary to understand unilateral renal function.

Unilateral upper urinary tract obstruction

Severe renal insufficiency

99mTc-DTPA dynamic renal scintigraphy

Glomerular filtration rate

C-reactive protein

Upper urinary tract obstruction (UUTO) is a common and challenging urinary disease caused by a variety of causes, such as ureteral junction obstruction, ureteral stones, ureteral strictures, urinary inflammation, tumors, etc., which often occur clinically in unilateral kidneys[1]. Most patients with urinary tract obstruction can resolve the obstruction after treatment[2]. However, persistent ureteral obstruction eventually leads to progressive glomerulosclerosis, tubulointerstitial fibrosis, and loss of renal function [3, 4]. For patients with severe renal insufficiency caused by obstruction, only by assessing the degree of damage caused by urinary tract obstruction to their renal function and grasping the prognosis of renal function recovery after obstruction is relieved can reasonable and effective treatment be provided for obstructive nephropathy.

At present, the degree of renal function impairment is often assessed by dynamic observation of serum estimated glomerular filtration rate (eGFR), and serum C-reactive protein is used to assess whether patients need preoperative anti-infective therapy. eGFR is readily available clinically and is often the first choice for assessing renal function[5]. However, patients with long-term unilateral upper urinary tract obstruction may have normal eGFR values due to compensation of contralateral renal function, which will provide inaccurate clinical information and mistakenly believe that the patient's urinary tract obstruction does not cause renal function impairment[6]. The use of estimated GFR based on cystatin C has been shown to be effective in predicting mortality risk in patients with end-stage renal disease in different populations[7]. However, cystatin C levels are affected by thyroid function, glucocorticoid levels, and the incidence of rectal cancer and melanoma[8].

For patients with severe renal insufficiency, radiographic images often have secondary signs of obstruction, at which time ^99mTc-diethylenetriaminepentaacetic acid (^99mTc-DTPA) dynamic renal scintigraphy can not only assess renal blood supply, but also accurately measure the renal function of total kidney and the divided kidney, and effectively assess the degree of renal impairment in patients[9, 10].

This study aimed to investigate whether the clinical information such as age, preoperative glomerular filtration rate, whether there was co-infection, location of obstruction and course of the disease could be used as influencing factors for renal function recovery after treatment of UUTO severe renal insufficiency.

Clinical data

This study was approved by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University (batch number: 2022-K175).

A retrospective analysis was performed on patients with unilateral upper urinary tract obstruction treated in urology after nuclear renal dynamic imaging in our hospital from January 2014 ~ January 2023.

Inclusion criteria: (1) unilateral upper urinary tract obstruction, (2) nuclear renal dynamic imaging before treatment, (3) severe impairment of renal function (Using the Gates method processing on SPECT [11]), 10ml (min/1.73m²) ≤ GFR ≤ 15ml (min/1.73m² )were rated as severely impaired according to the renal function curve and ^99mTc-DTPA dynamic renal scintigraphy results), (4) serum eGFR was checked in patients before and after treatment.

Exclusion Criteria: (1) impaired renal function or upper urinary tract obstruction on the healthy side, (2) impaired renal function due to non-obstructive factors, (3) upper urinary tract obstruction caused by factors other than the urinary system, (4) severe heart and lung disease and other chronic kidney diseases.

The patient inclusion process is shown in Fig. 1:

Laboratory tests and functional scintigraphy

The GFR value obtained by ^99mTc-DTPA dynamic renal scintigraphy and serum C-reactive protein were collected before treatment, and serum eGFR was collected three times before treatment and after treatment (within 1–3 months). Since some patients only had serum creatinine results, the CKD-EPI creatinine equation was used to calculate eGFR[12]. In this study, the change value of GFR (GFRd) before and after treatment was used as an indicator to evaluate the efficacy of treatment, which was defined as the difference between eGFR 1–3 months after treatment and before treatment. The main reason for choosing this indicator is that the patients included in this study had normal unaffected renal function before treatment and had a short follow-up time, so there was basically no change in unaffected renal function during the follow-up period.

The ^99mTc-DTPA dynamic renal scintigraphy instrument adopts single-photon emission computed tomography (SPECT) from GE, Discovery NM-670, and is equipped with a low-energy general-purpose collimator. ^99mTc is provided by Beijing Atomic Hi-Tech Co., Ltd., and the DTPA is provided by Beijing Xinke star Pharmaceutical Technology Co., Ltd., and the purity of radiotherapy after marking is 95%. The patient drank 300–500 ml of water 30 minutes before the examination, took the flat lying on the back position to collect images, and the patient's position remained motionless during the examination, and the probe field of view included both kidneys, ureters and bladder. The acquisition procedure is started immediately after the "projectile" injection of approximately 29.6–37.0 MBq/kg (0.8-1.0 mCi/kg) of the imaging agent ^99mTc-diethylenetriaminepentaacetic acid (^99mTc-DTPA) through the elbow vein. The energy peak is 140 keV, the matrix is 64×64, the window width is 20%, and the magnification is 1.33x. Dual phases dynamic acquisition, Phase 1 is the blood perfusion phase 2s/frame, a total of 30 frames; Phase 2 is the functional phase, that is, the uptake and excretion phase, 1 min/frame, a total of 15 frames. Using the SPECT Xeleris post-processing workstation, the kidney analysis software was used to manually outline the contours of both kidneys on the functional image as the region of interest (ROI), and the GFR values of the left and right kidneys were calculated by the Gates method [11].

Interpretation of results

Normally contralateral renal function is defined as having a GFR higher than or equal to the unilateral GFR of the normal participant in that age group. Severe unilateral renal impairment is defined as the GFR of the affected kidney being less than one-third of the GFR of normal participants in this age group. The changes in GFRd after treatment were divided into three groups, GFRd ≥ 5 ml(min•1.73m²)after treatment was improved renal function, GFRd < ± 5 ml（min•1.73m²）was no change after treatment, and GFRd >-5 ml（min•1.73m²） decreased after treatment [13]。

Statistical methods

Excel is used to organize the data, and R software (http://www.r-project.org) is used to perform statistical analysis on the obtained data. The number of predictors was controlled according to the ratio of the sample size of the participants to the number of predictors ≥ 10[14]. Age, body mass index, eGFR before treatment, GFR value obtained by ^99mTc-DTPA dynamic renal scintigraphy before treatment, and C-reactive protein before treatment were used as predictors (see Table 1). Multiple linear regression analysis was used to predict the GFRd value (predicted variable) after treatment. Moreover, the multicollinearity test and homogeneity of variance test were performed on the data, and the difference was statistically significant with P < 0.05.

Table 1

Descriptive statistics for predictors
Predictors		SD	Max
Age	48.7	14.6	87	20
Body mass index	23.5	2.8	30.4	16.5
eGFR before treatment	75.9	27.0	132.8	14.1
GFR of the affected kidney	11.76	5.43	21.9	1.21
C-reactive protein	15.7	30.0	160	0.41

In addition to exploring the effects of continuous variables, we grouped patients by gender (male, female) and site of obstruction (Ureters, kidneys, ureters combined with kidneys). At the same time, eGFR was divided into normal (> 90 ml/(min•1.73m²) and damaged (≤ 90 ml/(min•1.73m²) groups for analysis, and the difference of GFRd between the groups was calculated by two-sample t-test or one-way ANOVA according to the grouping situation, and the difference was statistically significant with P < 0.05.

Subject characteristics

A total of 153 patients with unilateral upper urinary tract obstruction with severe renal impairment were included in this study, including 84 men and 69 women. The age range is 20 ~ 87 years old, and the average age is 48.7 ± 14.6 years old; The remaining predictor statistics are shown in Table 1. According to the location and etiology of obstruction, there were 39 cases of ureteral stones, 23 cases of ureteral stenosis or atresia, 43 cases of kidney stones, and 48 cases of ureteral combined kidney stones.

Treatment

Of the 153 patients, 144 underwent surgery, of which 35 underwent ureteroscopy + stenting; 20 cases of ureteral balloon dilation + stent implantation; 17 cases of ureteral atresia segment anastomosis + ureteral bladder replantation; 30 cases of transureteral flexible lithotripsy + ureteral stent implantation; 21 cases underwent nephrectomy; 21 cases of ostomy. Another 9 patients underwent conservative treatment, of which 3 were terminated due to ureteral atresia stenosis, 3 were delayed due to family refusal of surgery, 1 was delayed because the patient needed to deal with other diseases first, and 2 were treated with anti-infection only due to severe infection symptoms.

In this study, 53 patients had improved kidney function after treatment, 43 had no significant change in kidney function, and 57 had further decreased kidney function after treatment.

Efficacy factors predict outcomes

According to the results of multiple linear regression, the goodness of fit of the model was R² = 0.3569, and the test result of the multiple regression equation was F = 5.106 (P = 0.0008), indicating that the overall linear relationship between the predicted variables and the five predictors in the model was statistically significant. Through optimal subset regression screening features, it was found that the prediction model had the best prediction effect when the variables were only the GFR value of the affected kidney obtained by ^99mTc-DTPA dynamic renal scintigraphy and serum C-reactive protein (Fig. 2a). Moreover, the GFR value of the kidneys obtained by ^99mTc-DTPA dynamic renal scintigraphy (P = 0.0262) and serum C-reactive protein (P = 0.0005) had a significant effect on the change of renal function after treatment, compared with age, body mass index, and eGFR before treatment (Table 2).

Table 2

Multiple regression results of efficacy and influencing factors of obstructive severe renal insufficiency.
Variables	coef	Std. Err.	t	Pr >\|t\|
Age	-0.15097	0.13360	-1.130	0.26435
BMI	0.45612	0.55628	0.820	0.41648
eGFR	-0.10484	0.06969	-1.504	0.13933
GFR of the affected kidney	0.61871	0.26932	2.297	0.02620 *
C-reactive protein	0.25347	0.06764	3.748	0.00050 ***
Note: The eGFR in this table is the patient's pre-treatment eGFR; The GFR of the affected kidney
obtained by ^99mTc-DTPA dynamic renal scintigraphy; Distinctive markers: P < 0.05, P < 0.01, **P < 0.001.

In order to further test the accuracy of multiple regression equations, a multicollinearity test was performed in this study (Fig. 2b). The results suggested that a strong negative correlation between the eGFR before treatment and age (r = -0.62), and there was no significant correlation between the remaining variables. However, since age had no significant effect on the predicted variables after feature screening, it had no effect on the interpretation of the results. In addition, the homogeneity test of variance (BP = 0.0956, P = 0.9533) indicated that the residuals of the predicted variables did not change with the change of the value levels of all predictors, which further verified the predictive ability of the multiple linear regression model.

Analysis of differences between groups

Table 3 compares the effects of sex, eGFR, and obstruction site on GFRd by group. The results showed that the mean value of GFRd in men was higher than that in women, the mean value of GFRd in patients with renal obstruction was higher than that in patients with ureteral obstruction, and the mean value of GFRd in patients with normal serum eGFR was lower than that of patients with reduced eGFR, but there was no statistically significant difference between the above three factors (P > 0.05).

Table 3

Differences in GFRd after treatment in different groups of patients
Variables	Groups	Patients		Effective treatment	F/t	P-value
Gender	male	84	0.56	29	0.19	0.85
Gender	female	69	-0.21	27
eGFR	> 90	84	1.14	30	0.72	0.48
eGFR	≤ 90	69	-1.24	26
Obstruction Site	ureter	62	1.12	29	0.06	0.81
	kidney	43	-2.90	23
	ureters + kidneys	48	0.81	24
Note: GFRd refers to the difference between the eGFR 1–3 months post-treatment and pre-treatment serum estimates; Effective treatment refers to the "GFRd ≥ 5 ml(min•1.73m²) mentioned in the Interpretation of results"

UUTO is a frequent and common disease in urology. Clinically, patients often miss the best period for treatment due to the lack of obvious symptoms in the early stage, and the renal function of the affected side has been seriously damaged when seeking medical treatment[15]. Among them, patients with severe unilateral renal function caused by upper urinary tract obstruction often relapse multiple times after treatment, resulting in prolonged course of the disease, which is more difficult to treat than ordinary mild upper urinary tract obstruction, and clinicians urgently need to clarify the efficacy factors before treatment[16]. This study concluded that the GFR value of the affected kidney obtained by ^99mTc-DTPA dynamic renal scintigraphy and serum C-reactive protein were effective factors affecting GFRd before and after treatment in patients with severe renal impairment caused by unilateral upper urinary tract obstruction, which was basically consistent with previous studies.

The risk of kidney infection in UUTO patients comes from failure to receive prompt treatment without obvious clinical symptoms[17]. Studies have shown that even if a patient's infection is well controlled before treatment, its treatment effect may be greatly reduced, suggesting that infection may be a factor in the patient's efficacy [18, 19]. C-reactive protein is the main indicator of systemic infection, and although patients in this study were treated with anti-infection before surgery, C-reactive protein is still the most significant influencing factor among all factors. This result suggests that once infection develops, efficacy is compromised. However, whether the effect of C-reactive protein can exceed the GFR value of the kidney needs to be further clarified after prospective studies control other influencing factors in patients.

It is worth noting that multiple linear regression analysis suggested that eGFR values did not guide the prediction of renal function recovery after treatment in patients with severe renal impairment caused by unilateral upper urinary tract obstruction. It is well known that preoperative eGFR level is the main indicator for clinical evaluation of renal function level, but 64% of patients with severe renal impairment caused by unilateral upper urinary tract obstruction included in this study did not have abnormal serum eGFR. This is mainly due to the compensatory increase in renal function on the unaffected side, which does not truly reflect the patient's impaired renal function (Fig. 3). In order to further evaluate the clinical value of serum estimated GFR, this study divided serum GFR before treatment into normal and functional decline groups, and found that the average GFRd value after treatment in the group of patients with normal eGFR before treatment was slightly higher than that in the hypofunctional group, but the difference was not significant. In clinical practice, many patients may have long-term asymptomatic state, and the course of the patient's disease cannot be determined by asking the medical history. Therefore, serum eGFR values are less significant when unilateral renal function is impaired or it is necessary to understand unilateral renal function. This further proves that ^99mTc-DTPA dynamic renal scintigraphy has considerable advantages in evaluating renal function in patients with severe renal insufficiency, and that ^99mTc-DTPA dynamic renal scintigraphy is irreplaceable in the evaluation of unilateral renal function. In addition, 30% of the patients in this study had a GFRd value of more than 5 ml (min•1.73 m²), indicating improvement in renal function. This result is defined by the level of eGFR change before and after treatment. According to the results of this study, the GFR value of the affected kidney obtained by ^99mTc-DTPA dynamic renal scintigraphy may be more intuitive as a predictor of renal function recovery. However, more clinical data is needed to support this in order to gain the trust of clinicians to perform ^99mTc-DTPA dynamic renal scintigraphy to dynamically assess the real-time renal function of the patient's unilateral kidney both before and after treatment.

For the location and sex of obstruction, there were significantly more male patients than women, and significantly more patients with ureteral obstruction than patients with obstruction due to kidney stones. Changes in renal function after treatment showed a higher mean GFRd in men and patients with ureteral obstruction than in the other group, suggesting that we may need to focus on women and patients with renal stones in the clinic. However, after statistical analysis, the difference between gender and obstruction site caused by GFRd was not significant, and it is necessary to prospectively include a larger sample size to further explore the influence of obstruction site and sex. In addition, the course of the disease and the surgical level of the surgeon were not analyzed, because the course of the disease is long and the onset is insidious and the time of disease cannot be calculated, and the surgical level of the surgeon is difficult to qualitatively or quantitatively. Secondly, this study is retrospective, resulting in incomplete records of some data.

In summary, this study found that the GFR value obtained by ^99mTc-DTPA dynamic renal scintigraphy and serum C-reactive protein in patients with severe renal impairment caused by unilateral upper urinary tract obstruction were significant influencing factors for the recovery of GFR after treatment, and the role of ^99mTc-DTPA dynamic renal scintigraphy was irreplaceable when unilateral renal function was impaired or it was necessary to understand unilateral renal function.

Fund:

In-hospital Cultivation Fund of the First Affiliated Hospital of Chongqing Medical University (PYJJ2021-15)

Disclosure:

The authors report no conflicts of interest in this work.

Author contributions:

Study concept and design, Data acquisition and analysis, Drafting of manuscript: Jia Li; Critical revision of the manuscript: Wenbo Li, Hua Pang.

Sorokin I, Mamoulakis C, Miyazawa K, Rodgers A, Talati J and Lotan Y. Epidemiology of stone disease across the world. World Journal of Urology. 2017.
Cozma C, Georgescu D, Popescu R, Geavlete B and Geavlete P. Double-J stent versus percutaneous nephrostomy for emergency upper urinary tract decompression. Journal of medicine and life. 2023; 16(5):663-667.
Yang J, Sun B, Min H, Son Y, Kim T, Lee J, Oh S, Kim M, Cho W, Ahn S, Ko G, Kwon Y, Cha J, Kang Y, Cha D and Jo S. Impact of acute kidney injury on long-term adverse outcomes in obstructive uropathy. Scientific reports. 2021; 11(1):23639.
See EJ, Jayasinghe K, Glassford N, Bailey M, Johnson DW, Polkinghorne KR, Toussaint ND and Bellomo R. Long-term risk of adverse outcomes after acute kidney injury: a systematic review and meta-analysis of cohort studies using consensus definitions of exposure. Kidney international. 2019; 95(1):160-172.
Kaufman DPB, H.; Knohl, S.J. . Physiology, Glomerular Filtration Rate (GFR) -- StatPearls. 2018.
Levey AS, Titan SM, Powe NR, Coresh J and Inker LA. Kidney Disease, Race, and GFR Estimation. Clinical journal of the American Society of Nephrology : CJASN. 2020; 15(8):1203-1212.
Vandecasteele S and De Vriese A. Cystatin C versus creatinine for kidney function-based risk. The New England journal of medicine. 2013; 369(25):2458-2459.
Inker L, Eneanya N, Coresh J, Tighiouart H, Wang D, Sang Y, Crews D, Doria A, Estrella M, Froissart M, Grams M, Greene T, Grubb A, Gudnason V, Gutiérrez O, Kalil R, et al. New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. The New England journal of medicine. 2021; 385(19):1737-1749.
Kravchick S, Stepnov E, Lebedev V, Linov L, Leibovici O, Ben-Horin C, Trejo L, Peled R and Cytron S. Non-contrast computerized tomography (NCCT) and dynamic renal scintigraphy (DRS) in the patients with refractory renal colic. European journal of radiology. 2006; 58(2):301-306.
Qisheng, Yang, Changyin, Wang, Chun, Gao, Wasili, Maimaiti, Shun and Linglong. Does baseline renal function always decrease after unilateral ureteral severe obstruction? -experimental validation and novel findings by Tc-99m diethylene triamine pentaacetate acid (DTPA) dynamic renal scintigraphy. Quantitative imaging in medicine and surgery. 2019; 9(8):1451-1465.
Russell C and Dubovsky E. Gates method for GFR measurement. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 1986; 27(8):1373-1374.
Inker LA, Eneanya ND, Coresh J, Tighiouart H, Wang D, Sang Y, Crews DC, Doria A, Estrella MM, Froissart M, Grams ME, Greene T, Grubb A, Gudnason V, Gutiérrez OM, Kalil R, et al. New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. N Engl J Med. 2021; 385(19):1737-1749.
Inker LA and Titan S. Measurement and Estimation of GFR for Use in Clinical Practice: Core Curriculum 2021. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2021; 78(5):736-749.
Riley R, Ensor J, Snell K, Harrell F, Martin G, Reitsma J, Moons K, Collins G and van Smeden M. Calculating the sample size required for developing a clinical prediction model. BMJ (Clinical research ed). 2020; 368:m441.
Xiong SW, Wang J, Zhu WJ, Cheng SD and Zhou LQ. Advance in re-do pyeloplasty for the management of recurrent ureteropelvic junction obstruction after surgery. Beijing da xue xue bao Yi xue ban = Journal of Peking University Health sciences. 2020; 52(4):794-798.
Washino S, Hosohata K and Miyagawa T. Roles Played by Biomarkers of Kidney Injury in Patients with Upper Urinary Tract Obstruction. International journal of molecular sciences. 2020; 21(15).
Onen A. Grading of Hydronephrosis: An Ongoing Challenge. Frontiers in pediatrics. 2020; 8:458.
Noakes M, Keogh, JB, Foster, PR, Clifton, PM, AF Noakes, M, Keogh, JB, Foster, PR, Clifton, PM. Cystatin-C and inflammatory markers in the ambulatory elderly. American Journal of Medicine. 2005; 118(12):1416.e1425-1416.e1431.
Chuang HH, Lin RH, Li WC, Yeh WC, Lin YA and Chen JY. High-Sensitivity C-Reactive Protein Elevation Is Independently Associated with Subclinical Renal Impairment in the Middle-Aged and Elderly Population—A Community-Based Study in Northern Taiwan. International Journal of Environmental Research and Public Health. 17(16).

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You are reading this latest preprint version

Analysis of efficacy factors in unilateral obstructive severe renal insufficiency

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Version 1

Abstract

Figures

Introduction

Materials and methods

Clinical data

Laboratory tests and functional scintigraphy

Interpretation of results

Statistical methods

Results

Subject characteristics

Treatment

Efficacy factors predict outcomes

Analysis of differences between groups

Discussion

Declarations

Fund:

Disclosure:

Author contributions:

References

Status:

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