Biphasic change in renal function after radical cystectomy and urinary diversion: Result from tertiary center in Thailand

Worapat Attawettayanon; Apiwich Anukoolphaiboon; Virote Chalieopanyarwong; Choosak Pripatnanont

doi:10.4103/UROS.UROS_102_20

ORIGINAL ARTICLE

Year : 2021 | Volume : 32 | Issue : 2 | Page : 59-63

Biphasic change in renal function after radical cystectomy and urinary diversion: Result from tertiary center in Thailand

Worapat Attawettayanon¹, Apiwich Anukoolphaiboon², Virote Chalieopanyarwong¹, Choosak Pripatnanont¹
¹ Department of Surgery, Division of Urology, Faculty of Medicine, Songklanagarind Hospital, Prince of Songkla University, Songkhla, Thailand
² Department of Surgery, Division of Urology, Faculty of Medicine, Songklanagarind Hospital, Prince of Songkla University, Songkhla; Department of surgery, Vachira Phuket Hospital, Phuket, Thailand

Date of Submission	13-Jul-2020
Date of Decision	01-Oct-2020
Date of Acceptance	29-Oct-2020
Date of Web Publication	22-Jun-2021

Correspondence Address:
Worapat Attawettayanon
Department of Surgery, Division of Urology, Faculty of Medicine, Songklanagarind Hospital, Prince of Songkla University, Songkhla 90110
Thailand

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/UROS.UROS_102_20

Abstract

Purpose: Radical cystectomy (RC) with urinary diversion has been established as the gold standard treatment for muscle invasive bladder cancer. This provides excellent local control and increases the survival rate. The postoperative renal function (RF) usually declines, especially with those with risky conditions such as increasing age, hypertension, diabetes, or the presence of preoperative hydronephrosis (HN). However, there are limited data about the potential preoperative factors to predict the postoperative RF following the RC. The current retrospective article aims at reviewing patients treated with RC with urinary diversion presenting demographics data, assessing the RF after performing the operation and identifying the associated factors that reduce the RF. Materials and Methods: Bladder cancer patients who underwent RC with a urinary diversion from January 2001 to December 2017 were reviewed. RF was assessed by using the estimated glomerular filtration rate (eGFR) through the MDRD formula. Multivariate analysis was performed to evaluate the association of the changing of RF. Results: One hundred and fifty-six patients were included in the study. The median age was 65 years (interquartile ranges [IQR] 57, 72), and the median follow-up time was 16.4 months (IQR 7.1, 33.4). Overall, 86 patients (55.12%) had HN at the initial treatment of RC. Baseline mean eGFR was 57.7 mL/min/1.73 m² (standard deviation [SD] = 23.7). The value of eGFR observed at 1, 12, and 60 months was 67.2 (SD = 29.5), 55.7 (SD = 26.3), and 55.8 (SD = 21.4) mL/min/1.73 m², respectively. At 1 month, female gender, no HN, and neobladder were independently associated with worse RF outcomes in both univariate and multivariate analysis (P < 0.05). The factors associated with eGFR under 60 mL/min/1.73 m² at 1 year were age, presence of HN, and adjuvant treatment. Conclusion: RF after cystectomy and urinary diversion improves for 1 month after the procedure, especially in patients with the presence of preoperative HN and then RF gradually decreases. There are no significant differences in preoperative and postoperative RF after a 5-year follow-up.

Keywords: Estimated glomerular filtration rate, radical cystectomy, renal function, urinary diversion

How to cite this article:
Attawettayanon W, Anukoolphaiboon A, Chalieopanyarwong V, Pripatnanont C. Biphasic change in renal function after radical cystectomy and urinary diversion: Result from tertiary center in Thailand. Urol Sci 2021;32:59-63

How to cite this URL:
Attawettayanon W, Anukoolphaiboon A, Chalieopanyarwong V, Pripatnanont C. Biphasic change in renal function after radical cystectomy and urinary diversion: Result from tertiary center in Thailand. Urol Sci [serial online] 2021 [cited 2023 Mar 29];32:59-63. Available from: https://www.e-urol-sci.com/text.asp?2021/32/2/59/318992

Introduction

Muscle invasive bladder cancer is a complex and aggressive disease associated with high morbidity and mortality rate. Each year, >430,000 new patients are diagnosed with bladder cancer worldwide.^[1] In Thailand, bladder cancer is the 8^th most common cancer, and the prevalence in males and females was 4.5/100,000 and 1.2/100,000, respectively.^[2] Radical cystectomy (RC) and bilateral pelvic lymphadenectomy with urinary diversion have been established as the gold standard treatment for muscle invasive bladder cancer.^[3] This provides excellent local control and increases the survival rate.^[4] Nevertheless, RC is associated with significant risks of perioperative and long-term morbidity and mortality.^[5],[6] Decreased renal function (RF) is observed in most patients after receiving RC. The etiology of decline in RF after RC is likely multifactorial, including age, recurrence of urinary tract infection, hypertension (HT), diabetes mellitus (DM), and presence of preoperative hydronephrosis (HN).^[7],[8],[9] Currently, several clinical guidelines recommend the usage of cisplatinum base as a perioperative systemic chemotherapy for patients with advanced-stage disease,^[10] but in order to use cisplatin as chemotherapy, the patient has to have good RF. Therefore, the maintenance of RF, or slow process development to chronic kidney disease (CKD) status, is an important issue for patients. However, there are limited data about the potential preoperative factors to predict postoperative RF following RC.^[11] This study investigates the long-term history of estimated glomerular filtration rate (eGFR) and detects the risk factors that affect RF.

Materials and Methods

Ethical approval for the study was obtained from the Human Research Ethical Committee of the Faculty of Medicine, Prince of Songkla University (62-085-10-1). The medical records of bladder cancer patients who were operated on in Songklanagarind Hospital from January 2001 to December 2017 were reviewed. The patients whose indications for RC included urothelial cell carcinoma or other cell type cancer with muscle-invasive bladder cancer without evidence of distant metastasis were 275. Patients whose age was lower than 18 years old patients whose preoperative analysis data were unavailable, incomplete, or patients who received ureterocutaneous urinary diversion were excluded. The final patient population consisted of 156 patients.

One hundred and fifty-six patients were identified and met all inclusion criteria. All data were obtained by reviewing the patient history, imaging studies, operative records as well as discharge summaries. Patients and factors which may be related to kidney function factors, including age at RC, gender, smoking history, concomitant comorbidity (DM and HT), body weight, height, body mass index (BMI), presence of HN, preoperative RF, type of urinary diversion (ileal conduit or ileal neobladder), pathological cell type, and tumor staging (T-stage), were reviewed. The RF was assessed by using the eGFR with the MDRD formula (GFR = 175 × Serum creatine^-1.154 age^-0.203 × 0.742 [if the patient was female]). Preoperative and postoperative eGFRs were calculated before RC as a baseline and eGFR at 1, 3, 6, 12, 24, 36, 48, and 60 months after surgery.

The statistical analysis was performed using the R software 3.6.3 (R Foundation for Statistical Computing, Vienna, Austria). Continuous variables were present as mean with standard deviation (SD) or as median with interquartile ranges (IQR). Categorical variables were presented as counts and percentages. Analyzed longitudinal data were used to generalized estimating equations. In univariate and multivariate logistic regression analyses were performed to identify the significant preoperative factors of postoperative eGFRs estimating the odds ratios and the 95% confidence interval. P < 0.05 (P < 0.05) was considered statistical significance.

Results

Patient characteristics

One hundred and fifty-six patients were treated with RC and urinary diversion from January 2001 to December 2017. The characteristics of the patients are shown in [Table 1]. Overall, 86 patients (55.12%) had HN at the initial treatment of RC. The median age was 65 years (IQR 57, 72), 137 patients (87.8%) were male. The median follow-up time was 16.4 months (IQR 7.1, 33.4). The pathological cell types were included urothelial carcinoma (n = 132, 88%), squamous cell carcinoma (n = 3, 2%), adenocarcinoma (n = 6, 4%), and other cell types (n = 15, 9.6%). After performing RC, 36 patients (23.1%) received adjuvant treatment with chemotherapy and 18 patients (11.5%) received radiation therapy.

Table 1: Demographics for patients undergoing radical cystectomy and urinary diversion

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Renal functions

[Figure 1] shows a trend in RF at initial treatment to even analysis at 5 years' postoperation. Baseline mean eGFR was 57.7 mL/min/1.73 m² (SD = 23.7). Improvement in eGFR was observed at 1 month after surgery, and mean eGFR was 67.2 mL/min/1.73 m² (SD = 29.5). After that, a decline in eGFR occurred, eGFR at 3, 6, 12, and 24 months was 59.8 (SD = 26.4), 54.4 (SD = 25.9), 55.7 (SD = 26.3), and 55.1 (SD = 25.4) mL/min/1.73 m², respectively shown as [Table 2]. The rate of change in eGFR at 1 year and 5 years after surgery compared to baseline were −3.37% and −3.29%, respectively, and no statistical significance was detected when comparing to the baseline.

Table 2: Estimated glomerular filtration rate at specific times, amount of change, and percentage of change from baseline

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Figure 1: Trend in renal function after radical cystectomy. eGFR = estimated glomerular filtration rate

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Factors influencing renal function

The variables associated with improving eGFR are reported in [Table 3]. Female gender, no preoperative HN, and neobladder were independently associated with worse renal outcomes in both univariate and multivariate analysis (P < 0.05), and an increase in BMI was associated with good RF after surgery at 1 month.

Table 3: Hazards ratio estimate and confidence intervals from proportional hazards modeling of improvement in estimated glomerular filtration rate at 1 month

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A decrease in eGFR was detected after following up with patients after >1 month. Regression analyses, including age, sex, BMI, presence of HN, type of urinary diversion, T-stage, and adjuvant treatment variables, were performed to determine the factors associated with eGFR under 60 mL/min/1.73 m² at 1 years. Age, presence of HN, and adjuvant treatment were independently associated with worse RF outcomes at 1 years, as demonstrated in [Table 4].

Table 4: Hazards ratio estimate and confidence intervals from proportional hazards modeling of deterioration in estimated glomerular filtration rate at 1 year

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Discussion

Deterioration of RF after RC is an important issue. Recent evidence demonstrated the association between severe CKD and all-cause mortality maintenance of eGFR is a major concern for survival.^[12] The rate of decline in RF after RC and urinary diversion ranges from 20% to 70%.^[9] Makino et al.^[13] reported the outcome of a patient after RC and urinary diversion who developed rapid deterioration of RF during the 1^st year and a gradual decline in function. Rouanne et al.^[14] also reported patients who had a lifelong risk of CKD after surgery. However, several reports showed a decline in RF immediately, which later was stabilized within 1–2 months.^[15] In contrast to previous evidence, the current study found a significant improvement in RF 1 month after the procedure. The hypothesis of this result may depend on the characteristics of the patient. In this study, >50% of the patients had preoperative HN. This seems to be a high percentage when compared to previous studies which reported a percentage from 9% to 25%.^{[13],[14],[16],[17]} Another reason was tumor staging. This group of patients had more aggressive and higher stage tumors compared to other reports, as 59.2% of patients had tumor stages of 3–4, and most of them were presented with upper urinary tract obstruction at initial presentation.

Hatakeyama et al.^[18] reported cutaneous ureterostomy that showed a tendency of better RF postoperatively compared to other urinary diversions, but no significant differences in pre- and postoperative RF at 5-year follow up were reported. This result was similar to the result of the present study as the median for 1 and 5-year eGFR decreased to 3.47% and 3.29% respectively. The type of urinary diversion was not associated with the deterioration of RF. Additionally, common risk factors were identified. Those affecting RF after surgery included increasing age, preoperative HN, and adjuvant treatment. Such were independent factors that contributed to deteriorating RF during the 5-year follow-up.

Urinary diversion is associated with metabolic complications. One-half of patients with orthotopic neobladder needed some form of alkalinizing treatment, while metabolic abnormally occurred only 12.8% in the conduit group.^[9] The most important factor for developing metabolic acidosis is impaired RF.^[19] The serum electrolyte between neobladder and ileal conduit did not differ significantly after the operation.^[20] Whereas Miyake et al.^[21] retrospectively reviewed patients with muscle-invasive bladder cancer who underwent RC with ileal conduit and found only serum potassium significant increase at 1 year postoperatively.

Perioperative chemotherapy, especially neoadjuvant chemotherapy, is recommended for all patients with a higher stage to improve the overall survival rate.^[22],[23] In this group of patients, the rate of perioperative chemotherapy was 23.1%. This seems to be mismatched when compared to the amount of higher stage in the current study. The first presentation of the disease is the main limitation to comply with international standards for muscle-invasive bladder cancer treatment. More than half of patients had RF deterioration which excluded patients eligible for full dose cisplatin-based chemotherapy, while less toxic carboplatin-based regimen failed to show significant benefits in this setting. The more important part was that patients themselves were afraid and refused this type of systemic treatment both pre- and post-surgery.

The present study hypothesized that the MDRD equation could represent eGFR, as the plasma clearance is the clinical reference standard for GFR measurement. The MDRD equation has been validated in populations of patients with renal failure and kidney transplantation, and is accurate within 70% of the measured values.^[14],[24]

Nonetheless, the current study has several limitations. It is a 17-year retrospective study and had to depend on data collection of several types, from handwritten material to electronic medical recordings. There was no standard follow-up or imaging protocol. Some patients could not come as scheduled, the serum creatinine was not checked on a regular basis or monitored in this cohort. However, these data could be useful to decide on the best treatment strategy to predict patients likely to develop CKD.

Conclusion

RF after cystectomy and urinary diversion improves patients' condition 1 month after the procedure, especially in those with the presence of preoperative HN, before gradually decreasing the RF. There are no significant differences in pre- and post-operative RF after a 5-year follow-up. Preoperative HN, increased age, and adjuvant treatment represent potentially modifiable influencing factors associated with the decrease in RF.

Acknowledgments

Thank you Ms. Nannapat Pruphetkaew from epidemiology unit Prince of Songkla university for statistical analysis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Kamat AM, Hahn NM, Eistathiou JA, Lerner SP, Malmstrom PU, Choi W, et al. Bladder cancer. Lancet. 2016;388:2796-810.
2.	Loanapiwat B. Urologic cancer in Thalland. Jpn J Cin Oncol. 2015;45:1007-15.
3.	Lobo N, Mount C, Omar K, Nair R, Thurairaja R, Khan MS. Landmarks in the treatment of muscle-invasive bladder cancer. Nat Rev Urol 2017;14:565-74.
4.	Clark PE, Agarwal N, Biagioli MC, Eisenberger MA, Greenberg RE, Herr HW, et al. Bladder cancer. J Natl Compr Canc Netw 2013;11:446-75.
5.	Shabsigh A, Korets R, Vora KC, Brooks CM, Cronin AM, Savage C, et al. Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol 2009;55:164-74.
6.	Shimko MS, Tollefson MK, Umbreit EC, Farmer SA, Blute ML, Frank I. Long-term complications of conduit urinary diversion. J Urol 2011;185:562-7.
7.	Canter D, Viterbo R, Kutikov A, Wong YN, Plimack E, Zhu F, et al. Baseline renal function status limits patient eligibility to receive perioperative chemotherapy for invasive bladder cancer and is minimally affected by radical cystectomy. Urology 2011;77:160-5.
8.	Thompson RH, Boorjian SA, Kim SP, Cheville JC, Thapa P, Tarrel R, et al. Eligibility for neoadjuvant/adjuvant cisplatin-based chemotherapy among radical cystectomy patients. BJU Int 2014;113:E17-21.
9.	Amini E, Djaladat H. Long-term complications of urinary diversion. Curr Opin Urol 2015;25:570-7.
10.	Witjes JA, Compérat E, Cowan NC, De Santis M, Gakis G, Lebret T, et al. EAU guidelines on muscle-invasive and metastatic bladder cancer: Summary of the 2013 guidelines. Eur Urol 2014;65:778-92.
11.	Gondo T, Ohno Y, Nakashima J, Hashimoto T, Nakagami Y, Tachibana M. Preoperative determinant of early postoperative renal function following radical cystectomy and intestinal urinary diversion. Int Urol Nephrol 2017;49:233-8.
12.	Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004;351:1296-305.
13.	Makino K, Nakagawa T, Kanatani A, Kawai T, Taguchi S, Otsuka M, et al. Biphasic decline in renal function after radical cystectomy with urinary diversion. Int J Clin Oncol 2017;22:359-65.
14.	Rouanne M, Perreaud A, Letang N, Yonneau L, Neuzillet Y, Hervé JM, et al. Trends in renal function after radical cystectomy and ileal conduit diversion: New insights regarding estimated glomerular filtration rate variations. Clin Genitourin Cancer 2015;13:e139-44.
15.	Narita T, Hatakeyama S, Koie T, Hosogoe S, Matsumoto T, Soma O, et al. Presence of transient hydronephrosis immediately after surgery has a limited influence on renal function 1 year after ileal neobladder construction. BMC Urol 2017;17:72.
16.	Hamidi N, Suer E, Ozkidik M, Gokce MI, Ozturk E, Ozcan C, et al. Effect of treatment modality on long term renal functions in patients with muscle invasive bladder cancer. Urol J 2019;16:274-8.
17.	Eisenberg MS, Thompson RH, Frank I, Kim SP, Cotter KJ, Tollefson MK, et al. Long-term renal function outcomes after radical cystectomy. J Urol 2014;191:619-25.
18.	Hatakeyama S, Koie T, Narita T, Hosogoe S, Yamamoto H, Tobisawa Y, et al. Renal function outcomes and risk factors for stage 3b chronic kidney disease after urinary diversion in patients with muscle invasive bladder cancer [corrected]. PLoS One 2016;11:e0149544.
19.	Kim KH, Yoon HS, Yoon H, Chung WS, Sim BS, Ryu DR, et al. Risk Factors for Developing Metabolic Acidosis after Radical Cystectomy and Ileal Neobladder. PLoS One. 2016;11:e0158220.
20.	Cho A, Lee SM, Noh JW, Choi DK, Lee Y, Cho ST, et al. Acid-base disorders after orthotopic bladder replacement: comparison of an ileal neobladder and an ileal conduit. Ren Fail. 2017;39:379-84.
21.	Miyake M, Owari T, Tomizawa M, Matsui M, Nishibayashi N, Iida K, et al. Long-term Changes in Renal Function, Blood Electrolyte Levels, and Nutritional Indices After Radical Cystectomy and Ileal Conduit in Patients with Bladder Cancer. Urol J. 2019;16:145-51.
22.	Jue JS, Koru-Sengul T, Miao F, Kroeger ZA, Moore KJ, Alameddine M, et al. Timing of adjuvant chemotherapy and overall survival following radical cystectomy. Urol Oncol. 2020;38:75.e15-75.e22.
23.	Meeks JJ, Bellmunt J, Bochner BH, Vlarke NW, Daneshmand S, Galsky MD, et al. A systematic review of neoadjuvant and adjuvant chemotherapy for muscle-invasive bladder cancer. Eur Urol. 2012;62:523-33.
24.	Prigent A. Monitoring renal function and limitations of renal function tests. Semin Nucl Med. 2008;38:32-46.