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What happens to the preserved renal parenchyma after clamped partial nephrectomy?

  • Longbin Xiong,
  • Jane K. Nguyen,
  • Yulu Peng,
  • Zhaohui Zhou,
  • Kang Ning,
  • Nan Jia,
  • Jing Nie,
  • Dongxiang Wen,
  • Zeshen Wu,
  • Gustavo Roversi,
  • Diego Aguilar Palacios,
  • Emily Abramczyk,
  • Carlos Munoz-Lopez,
  • Jack A. Campbell,
  • Yun Cao,
  • Wencai Li,
  • Xuepei Zhang,
  • Zhisong He,
  • Xiang Li,
  • Jiwei Huang,
  • Jianzhong Shou,
  • Jitao Wu,
  • Minfeng Chen,
  • Xiaofeng Chen,
  • Jiaxuan Zheng,
  • Congjie Xu,
  • Wen Zhong,
  • Zaishang Li,
  • Wen Dong,
  • Juping Zhao,
  • Hailang Zhang,
  • Junhang Luo,
  • Jianye Liu,
  • Fanghu Sun,
  • Hui Han,
  • Shengjie Guo,
  • Pei Dong,
  • Fangjian Zhou,
  • Chunping Yu,
  • Steven C. Campbell,
  • Zhiling Zhang

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.

By Dr. Riccardo Bertolo

The manuscript published by Xiong et al. is a retrospective study evaluating kidney parenchyma histologic changes following partial nephrectomy (PN) and subsequent radical nephrectomy (RN). The aim is to assess functional outcomes regarding ischaemia time/type and patient co-morbidities.

This is a multicentric stakeholder database featuring 19 Chinese centres and Cleveland Clinic [PMID: 35058086]; a unique dataset providing information on a well-studied topic. Data of 65 patients who underwent PN for renal cell carcinoma and subsequent RN due to tumour ipsilateral recurrence were retrieved. For the purpose of the study, paraffin sections of non-neoplastic renal parenchyma were obtained for both PN and RN specimens and evaluated at > 5 mm away from the tumour in the case of PN, or more remotely in RN specimens.

A modified histologic score published by the Mayo Clinic was used to stratify chronic kidney disease (CKD) based on glomerular, tubular, interstitial and vascular status (0 to 12 points) [PMID: 28314581]. Predictive factors for a substantial increase of the CKD score (> 3) among demographic, clinicopathologic, and perioperative data (notably, including pre-existence of CKD, hypertension, and diabetes) were evaluated by logistic regression. Both cold and warm ischemia was used during PN. Heterogeneity about the surgical approach and the use of either warm or cold ischaemia according to surgeon’s preference represented another limitation.

As a result, the CKD-score was found increased in 47 patients (72%) after RN, of which 29 patients experienced substantial increase (> 3). Neither type and duration of ischaemia (≥ or ≤ 25 min) during PN nor  the interval between PN and RN did predict significant differences in the CKD-score. However, patients with hypertension, diabetes, and/or pre-existing CKD demonstrated a higher rate and extent of the increase in CKD-score (odds ratio: 3.53 [1.12– 11.1]).

This study by Xiong et al. does represent a further step forward in contradicting the urological dogma that minimisation of renal ischemia must be the main focus of the surgeon approaching nephron sparing surgery. Heterogeneity on surgical approach and ischaemia type use according to surgeon’s preference represent some limitation. However, the strength of the study relies on the pathological analysis demonstrating no extended CKD features and gravitating towards patients features as main key players. Other prior studies by Parekh et al had demonstrated by pathological analysis on electronic microscopy, that long periods of ischaemia (over 60 min) had no impact on patient’s ultimate renal function.

Actually, several recent randomised studies did demonstrate that techniques to minimise ischaemia do not translate into objectively superior functional outcomes in comparison to the traditional global ischaemia provoked by clamping the main renal artery [PMID: 30659901, 33931361 34086393]. Rather, within acceptable ischaemia time intervals, the non-modifiable patient’s factors are ultimately impacting on renal function.

Other modifiable surgical factors beyond ischaemia time, such as resection techniques and renorrhaphy techniques (that unfortunately remained not investigated within the setting of the present study) do count more in determining the postoperative renal function. Let’s say a challenging renal mass is “resectable” attempted by an experienced surgeon, eventually with the aid of robotics and modern advanced image guidance technologies, fear of a long ischaemia time should not discourage surgeons from sparing the kidney unit.

Overall,  whenever PN indication is imperative, then it is a feasible and a reasonable option, however, functional outcomes are predicted by patients co-morbidities such as hypertension, diabetes and chronic kidney disease, rather than duration and mode of ischaemia.