
==== Front
Heliyon
Heliyon
Heliyon
2405-8440
Elsevier

S2405-8440(24)12656-4
10.1016/j.heliyon.2024.e36625
e36625
Research Article
Comparison of renal function of patients after tumor nephrectomy versus donor nephrectomy: Long term outcome using a propensity score matching analysis
Laksanabunsong Pongsatorn
Hansomwong Thitipat
Suk-ouichai Chalairat
Woranisarakul Varat
Jitpraphai Siros
Chotikawanich Ekkarin
Taweemonkongsap Tawatchai thawatchai.taw@mahidol.ac.th
⁎
Division of Urology, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, Thailand
⁎ Corresponding author. thawatchai.taw@mahidol.ac.th
20 8 2024
15 9 2024
20 8 2024
10 17 e3662510 8 2023
19 8 2024
20 8 2024
© 2024 The Authors
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).
Objective

To compare long-term incidence rate of chronic kidney disease (CKD) in patients after tumor nephrectomy (TN) and donor nephrectomy (DN) and to evaluate risk factors for developing CKD.

Materials and methods

Data from 1048 patients who performed TN (552) and DN (496) between 2000 and 2018 at Siriraj hospital were retrospectively analyzed. We obtained 106 patients for each group after using a 1:1 propensity score matching by age and preoperative glomerular filtration rate (GFR). The incidence rate of CKD and risk factors for CKD stage ≥3 were evaluated.

Results

There were no differences in incidence of CKD between TN (26.4 %) and DN group (24.5 %) with median follow-up time of 4.95 and 6.05 years (p = 0.308). There were no differences in mean GFR postoperatively at up to ten years follow-up (p = 0.378). The GFR at last follow-up was 71.15 and 68.1 ml/min/1.73 m2 in TN and DN groups (p = 0.172). The TN showed more proteinuria than DN group but not for postoperative hypertension. The multivariate analysis showed age 47 years (p = 0.012) and preoperative GFR 100 (p = 0.001) as a risk factor for developing CKD after nephrectomy but not for type for nephrectomy (p = 0.753).

Conclusion

The risk of developing CKD in patients after tumor nephrectomy was the same as in living kidney donors who were matched by age and preoperative GFR. Age over 47 years and preoperative GFR <100 of patients should be considered risk factors for developing CKD in patients choosing nephrectomy as the treatment of choice.

Keywords

Renal function
Chronic kidney disease
Nephrectomy
Donor
Renal cell carcinoma
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pmc1 Introduction

The gold standard for treatment in localized renal cell carcinoma was surgical removal of the tumor. Since postoperative renal function depends on the number of remaining nephrons, surgeons tend to perform a partial nephrectomy to preserve as many nephrons as possible.

However, some patients are still indicated for radical nephrectomy or tumor nephrectomy. According to several studies, patients with tumor nephrectomy had an increased risk of developing chronic kidney disease (CKD). Therefore, preoperative evaluation and selection of surgical treatment were very important for surgeons. Currently, there are no certain conclusions about whether tumor nephrectomy procedures by themselves or patient risk factors such as age, preoperative glomerular filtration rate (GFR), diabetes, hypertension, etc., caused the development of CKD in patients who underwent tumor nephrectomy.

In a previous study, most patients after donor nephrectomy had preserved GFR, normal albumin excretion, and excellent quality of life. Survival and risk of end stage renal disease (ESRD) in carefully selected kidney donors appear similar to those of the general population [1].

Age and preoperative GFR were the known risk factors for developing CKD in several studies [2,3]. Preoperative GFR less than 110 mg/ml/1.73 m2 and age more than 40 years were independent risk factors for decreased renal function after surgery [2]. Some studies show that patients who underwent tumor nephrectomy had a higher incidence risk of CKD compared to patients who underwent donor nephrectomy [2,4,5]. On the other hand, according to Marc-Olivier Timsit et al. study [3] and Wu FM et al., study [6], the renal function between patients after tumor nephrectomy and donor nephrectomy was compared. The result shows differently that tumor nephrectomy was not an independent risk factor for developing CKD. There was still controversy about the indication for nephrectomy, whether tumor nephrectomy or donor nephrectomy was an independent risk factor for CKD.

In addition, there was no long-term study in renal function after tumor nephrectomy compared to donor nephrectomy. We designed a study to compare the incidence rate of CKD between tumor nephrectomy patients and donor nephrectomy patients in long-term outcomes and demonstrated independent risk factors for developing CKD. In addition, we used pairs of patients matched by age and preoperative GFR to eliminate confounding factors, and this would be the first study in the Southeast Asian population.

2 Materials and methods

The study was approved by the Ethics Committee of Siriraj Institutional Review Board, Faculty of Medicine Siriraj Hospital, Mahidol University. In this retrospective cohort study, we included a total of 552 patients who underwent tumor nephrectomy (TN group) due to renal cell carcinoma and a total of 496 patients who underwent donor nephrectomy (DN group) between 1 January 2000 and 31 December 2018. All patients were at least 18 years old at the time of surgery and performed in our institute, Siriraj Hospital Mahidol University.

Patients who had a preoperative GFR of less than 60 ml/min/1.73 m2 or a follow-up period of less than one year were excluded from our study. Patients with renal cell carcinoma at least T3b or metastatic stage or had an abnormal contralateral kidney, including bilateral lesions and a single kidney, were also excluded.

There were 250 patients in the TN group and 429 patients in the DN group met our inclusion and exclusion criteria, as demonstrated in Fig. 1. The baseline patient characteristics, including age, sex, operative technique, comorbidities, nephrectomy site, smoking history and follow-up time were collected and compared as shown in Table 1. Age and preoperative GFR were known risk factors for the development of CKD in patients after nephrectomy by several studies [2,3]. In our study, there was a statistically significant difference between the TN group and the DN group in terms of age (57.1 vs. 37.4 years, p < 0.001) and preoperative GFR (85.8 vs. 107 ml/min/1.73 m2, p < 0.001), patients were matched one to one by propensity score using these two parameters to eliminate confounders.Fig. 1 Diagram of study

Diagram of study demonstrated inclusion and exclusion criteria of patient and showed number of patients after propensity score matching.

Fig. 1

Table 1 Patient characteristics at baseline.

Table 1Variables	Patients	TN group (250)	DN group (429)	P-value	
Mean (SD) Age, year		57.1 (11.5)	37.4 (10)	<0.001	
Gender	679			<0.001	
- Male

	302	156 (62.4 %)	146 (34 %)		
- Female

	377	94 (37.6 %)	283 (66 %)		
Mean (SD) Preoperative GFR		85.8 (17.1)	107 (14.7)	<0.001	
Smoking history		30 (12 %)	66 (15.4 %)	0.222	
Mean (SD) operative time, minute		184.4 (84.9)	227.9 (58)	<0.001	
Median (Q1-Q3) blood loss, ml		200 (100–500)	100 (50–200)	<0.001	
Operative technique	679			<0.001	
- Open

	278	146 (58.4 %)	132 (30.8 %)		
- Laparoscopy

	401	104 (41.6 %)	297 (60.2 %)		
Site	679			<0.001	
- Right

	208	116 (46.4 %)	92 (21.4 %)		
- Left

	471	134 (53.6 %)	337 (79.6 %)		
Preoperative HT		131 (52.4 %)	0	<0.001	
Preoperative DM		49 (19.6 %)	0	<0.001	
Median (Q1-Q3) follow up time, year		5.7 (3.1–9.2)
Range 1–20 years	6.0 (3.5–9.9)
Range 1–21.6 years	0.285	

After matching with the propensity score, there were 106 patients in the TN group and 106 patients in the DN group. To evaluate renal outcome, we collected postoperative GFR in several periods, including 3–6 months, one year, five years, 10 years postoperatively and at the time of the last follow-up. The GFR was calculated using the CKD-EPI equation and patients were stratified according to GFR categories in CKD [7]. Chronic kidney disease in our study was defined as CKD in at least stage 3 (GFR less than 60 ml/min/1.73 m2). Proteinuria and de novo hypertension were compared as markers for progression to CKD at the last follow-up time.

For analysis, we used an independent T-test and a Mann-Whitney test for continuous variables and used the Chi-square for category variables. During the univariate and multivariate analysis, age, body mass index, and preoperative GFR were classified into two groups according to the mean value. Univariate analysis was calculated using the Mantel-Haenszel odd ratio. Multivariate analysis was carried out using logistic regression analysis. All tests were two-tailed and a P-value less than 0.05 were considered statistically significant.

3 Results

After the patients were matched one to one by propensity score using age and preoperative GFR as parameters, there were 106 patients in the TN group and 106 patients in the DN group. The patient demographic data is shown in Table 2.Table 2 Demographic data after matching by propensity score.

Table 2Variables	Patients	TN group	DN group	P-value	
Mean (SD) Age,year		47.3 (7.6)	47.2 (7.6)	0.94	
Gender	212			<0.001	
- Male

	95	62 (58.5 %)	33 (31.1 %)		
- Female

	117	44 (41.5 %)	73 (68.9 %)		
Mean (SD) BMI		25.4 (5)	23.9 (3.2)	0.008	
Mean (SD) Preoperative GFR		97.8 (13.8)	98.5 (13.4)	0.69	
Smoking history		16 (15.1 %)	10 (9.4 %)	0.209	
Mean (SD) operative time, minute		190.7 (83.1)	226.5 (59.2)	<0.001	
Median (Q1-Q3) blood loss, ml		200 (100–500)	100 (50–200)	<0.001	
Operative technique				0.001	
- Open

	94	59 (55.7 %)	35 (33 %)		
- Laparoscopy

	118	47 (44.3 %)	71 (69 %)		
Site				0.001	
- Right

		46 (43.4 %)	24 (22.6 %)		
- Left

		60 (56.6 %)	82 (77.4 %)		
Preoperative HT		40 (37.7 %)	0	<0.001	
Preoperative DM		17 (16 %)	0	<0.001	
Median (Q1-Q3) follow up time, year		4.95 (3.6–9.7)
Range 1–20 years	6.05 (2.8–9.1)
Range 1–19.3 years	0.308	

There were no statistically significant differences in terms of age (p = 0.94), preoperative GFR (p = 0.69), follow-up time (p = 0.308) and smoking history (p = 0.210) between the TN group and the DN group. However, compared to the DN group, the TN group included more male patients (58.5 % vs. 31.1 %, p < 0.001), more BMI (25.4 vs. 23.9, p = 0.008), more open surgery (55.7 % vs. 33 %, p = 0.001), and more right-side nephrectomy (43.4 % vs. 22.6 %, p = 0.001). Furthermore, the patients in the TN group had more comorbid diseases, such as hypertension (37.7 %) and diabetes mellitus (16 %), while there were no patients with hypertension or diabetes mellitus in the DN group.

Renal function was compared in several postoperative periods by measuring GFR at 3–6 months, one year, five years, and ten years postoperatively. All postoperative periods did not show statistically significant differences in mean GFR, as shown in Table 3. The postoperative GFR at the last follow-up in the TN group and the DN group was 71.15 and 68.1 ml/min/1.73 m2, respectively. The overall incidence rate of CKD was 26.4 % in the TN group and 24.5 % in the DN group, which did not show significant differences with p = 0.753. In the subgroup based on the category of GFR, there was no difference in the incidence of CKD stage 3a, stage 3b, and stage 4. None of the patients developed CKD stage 5 or underwent hemodialysis in our study. Proteinuria was significantly increased in the TN group compared to the DN group (12.3 % vs 3.8 %, p = 0.023), while de novo hypertension after surgery between these two groups was not different (p = 0.925).Table 3 Renal function outcome.

Table 3Variables	TN group	DN group	P-value	
3–6 months postoperative GFR(n)	67.8 (75)	63.6 (91)	0.059	
 % GFR change	−30.7 %	−35.4 %		
1-year postoperative GFR(n)	70.3 (81)	65.6 (94)	0.087	
 % GFR change	−28.1 %	−33.4 %		
5-year postoperative GFR(n)	69.1 (44)	67.9 (52)	0.692	
 % GFR change	−29.3 %	−31.1 %		
10-year postoperative GFR(n)	74.8 (20)	70.7 (22)	0.378	
 % GFR change	−23.5 %	−28.2 %		
Final postoperative follow up GFR (Q1-Q3)	71.15 (59.1–86.775)	68.1 (60.1–77.55)	0.172	
Overall CKD n (%)	28 (26.4 %)	26 (24.5 %)	0.753	
- CKD stage 3a

	26 (24.5 %)	23 (21.7 %)	0.625	
- CKD stage 3b

	1 (0.9 %)	3 (2.8 %)	0.313	
- CKD stage 4

	1 (0.9 %)	0	0.316	
Proteinuria n (%)	13 (12.3 %)	4 (3.8 %)	0.023	
De novo hypertension n (%)	9 (13.6 %)	15 (14.2 %)	0.925	

From the univariate analysis, the risk factors for developing CKD at least stage 3 were male (OR 2.193, p = 0.014), age older than 47 years (OR 3.354, p < 0.001), smoking history (OR 2.439, p = 0.04), preoperative GFR less than 100 (OR 5.976, p < 0.001) while the indication for nephrectomy whether tumor nephrectomy or kidney donation, was not statistically significant risk factor (OR 1.105, p = 0.753) as shown in Table 4. For the multivariate analysis, the only significant risk factors were age more than 47 years (adjust OR 2.608, p = 0.012) and preoperative GFR less than 100 (adjust OR 4.042, p = 0.001), while gender and smoking history were not statistically significant risk factors.Table 4 Univariate and multivariate analysis of risk factors for CKD.

Table 4Variables	OR	95 % CI	P-value	Adjust OR	95 % CI	P-value	
Tumor nephrectomy vs donor nephrectomy	1.105	0.595–2.050	0.753	–			
Age (>47 vs ≤ 47 year)	3.354	1.71–6.576	<0.001	2.608	1.239–5.490	0.012	
Gender (male)	2.193	1.169–4.116	0.014	1.444	0.692–3.015	0.328	
Site (right)	0.91	0.469–1.766	0.781	–			
Preoperative HT	0.819	0.362–1.854	0.632	–			
Preoperative DM	1.671	0.587–4.758	0.337	–			
Smoking history	2.439	1.043–5.703	0.040	1.962	0.732–5.257	0.180	
Surgical technique (laparoscopy)	1.35	0.719–2.535	0.351	–			
BMI (>25 vs ≤ 25)	1.145	0.614–2.135	0.671	–			
Preoperative GFR (<100 vs ≥ 100)	5.976	2.807–12.723	<0.001	4.042	1.815–9.003	0.001	

4 Discussion

This study was a comparison of renal function or GFR in patients after tumor nephrectomy and donor nephrectomy. Nephrectomy had been found to decrease GFR and increase the risk of CKD, whether the indication for nephrectomy was renal cell carcinoma or kidney donation [5]. Previously, several studies showed that there was no difference in GFR during the first year of the postoperative period between these two groups [2,3,8] but the study by Sang Hyub Lee, which compared 79 patients with renal cell carcinoma to age-matched donor patients, showed that GFR started to be lower in the TN group than in the DN group after the second year of surgery [2]. We, therefore, explored the long-term renal outcome. In our study, the patient was followed postoperatively with a median follow-up time of 4.95 years in the TN group and 6.05 years in the DN group, the GFR decreased by 27.2 % and 30.8 %, respectively (p = 0.172). We found no significant differences in the change in GFR after nephrectomy at longer follow-up compared to previous studies.

According to Hassan N. Ibrahim's study, which determined the lifetime risk of 3698 kidney donor patients between 1963 and 2007, survival and risk of ESRD in carefully selected kidney donors appear to be similar to those of the general population [1]. However, patients after donor nephrectomy have an increased risk of chronic kidney disease, since 24.4 % of kidney donors progress to at least CKD stage 3 in the Tan et al. study [9]. The overall incidence rate of CKD in our study was 26.4 % in the TN group and 24.5 % in the DN group, which did not show significant differences with p = 0.753. According to the univariate analysis, there was no increase in the risk of CKD for tumor nephrectomy compared to donor nephrectomy in patients of the same age and preoperative GFR (OR 1.105 95%CI 0.595–2.05). Our result is consistent with the research by Marc-Olivier Timsit et al. who compared 124 patients who had localized renal cell carcinoma and underwent tumor nephrectomy with 124 patients who underwent living donor nephrectomy for four years. The incidence of CKD was not significant with p = 0.51 [3].

In addition to the change in GFR, nephrectomy can cause complications such as proteinuria or high blood pressure compared to the normal population [10,11]. We found that patients undergoing tumor nephrectomy developed more proteinuria (12.3 % vs. 3.8 %, p = 0.023), which is consistent with the study by Mohamed Etafy et al. that established proteinuria of 21 % and 0 % in kidney cancer patients and kidney donors, respectively [4]. However, the incidence of new hypertension after surgery in these two groups was not significant, 13.6 % in the TN group and 14.2 % in the DN group (p = 0.925) in our study. These parameters might be early markers for predicting the development of CKD in long-term outcomes.

The independent factor for predicting CKD is still controversial. From the previous study, the risk factor includes sex, BMI, indication for surgery, age, preoperative GFR, and comorbidities [[1], [2], [3],12]. Hypertension and diabetes mellitus were also risk factors for CKD [12]. Propensity score matching was employed in this study to account for age and preoperative GFR. However, even with this approach, factors such as adjuvant chemotherapy, medications, and existing comorbidities could still potentially bias the renal function outcomes in the tumor nephrectomy group.

Analysis of the tumor nephrectomy group revealed that 11 out of 106 patients received adjuvant chemotherapy due to distant metastasis. All patients receiving chemotherapy received tyrosine kinase inhibitors (TKI). A comparison of CKD development in patients who received TKI (n = 11) to those who did not (n = 95) suggests that adjuvant chemotherapy isn't a significant risk factor (OR = 1.05, p = 0.946).

We found a higher incidence of preoperative diabetes and hypertension in the TN group compared to the DN group. However, our study did not find preoperative hypertension and preoperative diabetes mellitus as risk factors for CKD, which is consistent with the Marc-Olivier Timsit study [3]. This may be due to the fact that the number of patients with these comorbidities is too small, especially in the DN group. In addition, among the 64 patients diagnosed with hypertension during the follow-up period (40 with pre-existing and 24 with de novo hypertension), 22 received Angiotensin converting enzyme inhibitor/Angiotensin II receptor blocker (ACEI/ARB) treatment. Notably, only 5 of these patients developed CKD. Comparing the development of CKD between those receiving ACEI/ARB (n = 22) and those who did not (n = 42) suggests that ACEI/ARB use was not associated with an increased risk of CKD (OR = 0.846, p = 0.957). These findings suggest that even in the presence of hypertension, ACEI/ARB treatment may not contribute to CKD development in this patient population.

Several studies had found that age and GFR before surgery were risk factors for CKD [2,3], which was correlated with our study. From our multivariate analysis, patients over 47 years of age (OR 2.608, 95%CI 1.239–5.490) and patients with preoperative GFR less than 100 (OR 4.042, 95%CI 1.815–9.003) had a significantly higher risk of CKD. These two factors should be considered as factors to select patients for nephrectomy.

The first limitation of this research on the research process is a retrospective study in nature. Second, even though propensity score matching was used, there were still differences in demographic data, including gender, site, and especially comorbidities in which hypertension and diabetes mellitus appeared more in the TN group. Lastly, to evaluate proteinuria, our study used a urine dipstick test, which was less sensitive and less accurate than urine microalbuminuria.

5 Conclusion

According to the results of our study in the South Asian population, the indication for nephrectomy, whether tumor nephrectomy or donor nephrectomy was not an independent risk factor for the development of CKD after surgery in the long-term. The incidence of CKD in patients after tumor nephrectomy was the same as in living kidney donors who were matched by age and preoperative GFR. Age older than 47 years and preoperative GFR less than 100 mg/ml/1.73 m2 of the patients were considered risk factors for developing CKD after nephrectomy.

Ethics statement

The study was approved by the Ethics Committee of Siriraj Institutional Review Board (593/2563(IRB2)), Faculty of Medicine Siriraj Hospital, Mahidol University.

Data availability

The data from this study are not deposited in a publicly available repository. However, the data will be made available upon request for academic purposes.

CRediT authorship contribution statement

Pongsatorn Laksanabunsong: Writing – review & editing, Writing – original draft, Validation, Formal analysis, Data curation. Thitipat Hansomwong: Validation, Data curation. Chalairat Suk-ouichai: Methodology, Data curation. Varat Woranisarakul: Formal analysis, Data curation. Siros Jitpraphai: Validation, Data curation. Ekkarin Chotikawanich: Writing – review & editing, Data curation. Tawatchai Taweemonkongsap: Writing – review & editing, Writing – original draft, Visualization, Validation, Supervision, Resources, Project administration, Methodology, Investigation, Formal analysis, Data curation, Conceptualization.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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