Longbin Xiong1, Jane K Nguyen2, Yulu Peng1, Zhaohui Zhou1, Kang Ning1, Nan Jia3, Jing Nie3, Dongxiang Wen4, Zeshen Wu1, Gustavo Roversi5, Diego Aguilar Palacios5, Emily Abramczyk5, Carlos Munoz-Lopez5, Jack A Campbell5, Yun Cao6, Wencai Li7, Xuepei Zhang7, Zhisong He8, Xiang Li9, Jiwei Huang10, Jianzhong Shou11, Jitao Wu12, Minfeng Chen13, Xiaofeng Chen14, Jiaxuan Zheng15, Congjie Xu15, Wen Zhong16, Zaishang Li17, Wen Dong18, Juping Zhao19, Hailang Zhang20, Junhang Luo21, Jianye Liu22, Fanghu Sun23, Hui Han1, Shengjie Guo1, Pei Dong1, Fangjian Zhou1, Chunping Yu24, Steven C Campbell25, Zhiling Zhang26. 1. Department of Urology, Sun Yat-Sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in Southern China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. 2. Department of Anatomic Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA. 3. State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China. 4. State Key Laboratory of Oncology in Southern China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. 5. Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA. 6. State Key Laboratory of Oncology in Southern China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, China. 7. Department of Urology, First Affiliated Hospital of Zhengzhou University, Henan, China. 8. Department of Urology, Peking University First Hospital, Beijing, China. 9. Department of Urology, West China Hospital of Sichuan University, Sichuan, China. 10. Department of Urology, Renji Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China. 11. Department of Urology, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China. 12. Department of Urology, Yantai Yuhuangding Hospital, Shandong, China. 13. Department of Urology, Xiangya Hospital of Central South University, Changsha, China. 14. Department of Urology, The First People's Hospital of Chenzhou, Hunan, China. 15. Department of Pathology, Hainan General Hospital, Hainan, China. 16. Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. 17. Department of Urology, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China; Department of Urology, The Second Clinical College of Jinan University, Shenzhen, China. 18. Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China. 19. Department of Urology, Ruijin Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China. 20. Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. 21. Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. 22. Department of Urology, The Third Xiangya Hospital of Central South University, Hunan, China. 23. Department of Urology, No. 1 Hospital of Lian Yungang, Jiangsu, China. 24. Department of Urology, Sun Yat-Sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in Southern China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. Electronic address: yuchp@sysucc.org.cn. 25. Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address: Campbes3@ccf.org. 26. Department of Urology, Sun Yat-Sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in Southern China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. Electronic address: zhangzhl@sysucc.org.cn.
Abstract
BACKGROUND: Most partial nephrectomies (PNs) are performed with hilar occlusion to reduce blood loss and optimize visualization. However, the histologic status of the preserved renal parenchyma years after PN is unknown. OBJECTIVE: To compare the histologic chronic kidney disease (CKD) score of renal parenchyma before and years after PN, and to explore factors associated with CKD-score increase and glomerular filtration rate (GFR) decline. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of 147 renal cell carcinoma patients who underwent PN and subsequent radical nephrectomy (RN) due to tumor recurrence was performed in 19 Chinese centers and Cleveland Clinic. Macroscopic normal renal parenchyma was evaluated at least 5 mm away from the tumor in PN specimens and at remote sites in RN specimens. INTERVENTION: PN/RN and ischemia. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Histologic CKD score (0-12) represents a summary of glomerular/tubular/interstitial/vascular status. Predictive factors for a substantial increase of CKD score (≥3) were evaluated by logistic regression. RESULTS AND LIMITATIONS: Sixty-five patients with all necessary data were analyzed. The median interval between PN and RN was 2.4 yr. Median durations of warm ischemia (n = 42) and hypothermia (n = 23) were both 23 min. The histologic CKD score was increased after RN in 47 (72%) patients, with 29 (45%) experiencing more substantial increase (≥3). There was no significant difference in the change of CKD score related to the type and duration of ischemia (p = 0.7 and p = 0.4, respectively) or interval from PN to RN (p > 0.9). However, patients with comorbidities of hypertension, diabetes, and/or pre-existing CKD (hypertension [HTN]/diabetes mellitus [DM]/CKD) demonstrated increased rate and extent of CKD-score increase. On univariate analysis, HTN/DM/CKD was the only predictor of a substantial CKD-score increase (odds ratio: 3.53 [1.12-11.1]). Decline of GFR was modest and similar between patients with/without a substantial CKD-score increase. CONCLUSIONS: Within the context of conventional, limited durations of ischemia, histologic deterioration of preserved parenchyma after PN appears to be primarily due to pre-existing medical comorbidities rather than ischemia. A subsequent decline in renal function was mild and independent of histologic changes. PATIENT SUMMARY: After clamped PN, the preserved renal parenchyma demonstrated histologic deterioration in many cases, which correlated with the presence of comorbidities such as hypertension, diabetes mellitus, or chronic kidney disease. In contrast, the type and duration of ischemia did not correlate with histologic changes after PN, suggesting that ischemia insult had only limited impact on parenchyma deterioration.
BACKGROUND: Most partial nephrectomies (PNs) are performed with hilar occlusion to reduce blood loss and optimize visualization. However, the histologic status of the preserved renal parenchyma years after PN is unknown. OBJECTIVE: To compare the histologic chronic kidney disease (CKD) score of renal parenchyma before and years after PN, and to explore factors associated with CKD-score increase and glomerular filtration rate (GFR) decline. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of 147 renal cell carcinoma patients who underwent PN and subsequent radical nephrectomy (RN) due to tumor recurrence was performed in 19 Chinese centers and Cleveland Clinic. Macroscopic normal renal parenchyma was evaluated at least 5 mm away from the tumor in PN specimens and at remote sites in RN specimens. INTERVENTION: PN/RN and ischemia. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Histologic CKD score (0-12) represents a summary of glomerular/tubular/interstitial/vascular status. Predictive factors for a substantial increase of CKD score (≥3) were evaluated by logistic regression. RESULTS AND LIMITATIONS: Sixty-five patients with all necessary data were analyzed. The median interval between PN and RN was 2.4 yr. Median durations of warm ischemia (n = 42) and hypothermia (n = 23) were both 23 min. The histologic CKD score was increased after RN in 47 (72%) patients, with 29 (45%) experiencing more substantial increase (≥3). There was no significant difference in the change of CKD score related to the type and duration of ischemia (p = 0.7 and p = 0.4, respectively) or interval from PN to RN (p > 0.9). However, patients with comorbidities of hypertension, diabetes, and/or pre-existing CKD (hypertension [HTN]/diabetes mellitus [DM]/CKD) demonstrated increased rate and extent of CKD-score increase. On univariate analysis, HTN/DM/CKD was the only predictor of a substantial CKD-score increase (odds ratio: 3.53 [1.12-11.1]). Decline of GFR was modest and similar between patients with/without a substantial CKD-score increase. CONCLUSIONS: Within the context of conventional, limited durations of ischemia, histologic deterioration of preserved parenchyma after PN appears to be primarily due to pre-existing medical comorbidities rather than ischemia. A subsequent decline in renal function was mild and independent of histologic changes. PATIENT SUMMARY: After clamped PN, the preserved renal parenchyma demonstrated histologic deterioration in many cases, which correlated with the presence of comorbidities such as hypertension, diabetes mellitus, or chronic kidney disease. In contrast, the type and duration of ischemia did not correlate with histologic changes after PN, suggesting that ischemia insult had only limited impact on parenchyma deterioration.