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Risks and benefits of partial nephrectomy performed with limited or with zero ischaemia time

  • Daniele Cignoli,
  • Giuseppe Basile,
  • Giuseppe Fallara,
  • Giuseppe Rosiello,
  • Federico Belladelli,
  • Francesco Cei,
  • Giacomo Musso,
  • Chiara Re,
  • Roberto Bertini,
  • Pierre Karakiewicz,
  • Alexandre Mottrie,
  • Federico Dehò,
  • Andrea Gallina,
  • Francesco Montorsi,
  • Andrea Salonia,
  • Umberto Capitanio,
  • Alessandro Larcher

To test the hypothesis that longer warm ischaemia time (WIT) might have a marginal impact on renal functional outcomes and might, in fact, reduce haemorrhagic risk intra-operatively.

Patients and Methods
Data from 1140 patients treated with elective partial nephrectomy (PN) for a cT1-2 cN0 cM0 renal mass were prospectively collected. WIT was defined as the duration of clamping of the main renal artery with no refrigeration and was tested as a continuous variable. The primary outcome of the study was evaluation of the effect of WIT on renal function (estimated glomerular filtration rate [eGFR]) postoperatively, at 6 months and in the long term (measured between 1 and 5 years after surgery). The secondary outcome of the study was haemorrhagic risk, defined as estimated blood loss (EBL) or peri-operative transfusions. Multivariable linear, logistic and Cox regression analyses, accounting for age, Charlson comorbidity index, clinical size, preoperative eGFR and year of surgery, were used and the potential nonlinear relationship between WIT and the study outcomes was modelled using restricted cubic splines.

A total of 863 patients (76%) underwent PN with WIT and 277 (24%) without. The baseline median eGFR was 87.3 (68.8–99.2) mL/min/1.73m2 for the on-clamp population and 80.6 (63.2–95.2) mL/min/1.73m2 for the off-clamp population. The median duration of WIT was 17 (13–21) min. At multivariable analyses predicting renal function, longer WIT was associated with decreased postoperative eGFR (estimate: −0.21, 95% confidence interval [CI] −0.31; −0.11 [P < 0.001]). Conversely, no association between WIT and eGFR was recorded at 6-month or long-term follow-up (all P > 0.8). At multivariable analyses predicting haemorrhagic risk, clampless resection with no ischaemia time and PN with short WIT was associated with an increased EBL (estimate: −21.56, 95% CI −28.33; −14.79 [P < 0.001]) and peri-operative transfusion rate (estimate: −0.009, 95% CI −0.01; −0.003 [P = 0.002]). No association between WIT and positive surgical margin status was recorded (all P = 0.1).

Patients and clinicians should be aware that performing PN with very limited or even with zero WIT might increase bleeding and the need for peri-operative transfusion while not improving long-term renal function outcomes.

Commentary by Dr. Riccardo Bertolo

The EAU guidelines nowadays suggest partial nephrectomy (PN) as the gold standard surgical treatment for cT1 renal tumours [1]. A plethora of studies has focused on the key determinants of postoperative functional outcomes [2].

If renal ischaemia has historically been one of the most important drivers of the early renal functional impairment after PN, growing evidence has suggested that type and duration of ischaemia have far less influence on long-term renal function compared to other factors [3].

Most of us likely had the chance to read the negative results of three recently published trials about off-clamp and selective ischemia, suggesting that minimised ischemia techniques did not show any benefit in terms of renal function over global clamping [4].

With their analysis on a cohort of 1140 patients, Cignoli and colleagues aimed to evaluate once again the impact of management of renal hilum and warm ischemia time in on-clamp cases on renal function. Moreover, the authors tested (again) the hypothesis that zero-ischaemia techniques might increase the risk of haemorrhagic bleeding and the rate of positive surgical margins.

Overall, on-clamp technique was performed in 863 patients (76%), with a median (interquartile range [IQR]) of 17 (13–21) minutes of warm ischemia, while 277 patients (24%) underwent off-clamp PN. The latter cohort had worse eGFR at baseline (median [IQR] 80.6 [63.2–95.2] mL/min/1.73m2 vs 87.3 [68.8–99.2] mL/min/1.73m2 (p < 0.001) and more comorbidities according to the Charlson’s index. This likely selected such patients for off-clamp during the three decades considered.

As a result, longer ischemia time was associated with decreased early postoperative eGFR, but no relationship between ischemia time and renal function was found either at the 6-month or longer-term follow-up. This confirms previous findings suggesting that most patients recover within a few months from surgery after an eventual ischemic injury.

Contradicting the findings from recent randomised studies, estimated blood loss was higher in the off-clamp group (400 [150–700] mL vs 200 [100–450] mL; p < 0.001), as was the peri-operative transfusion rate (26% vs 18%, p = 0.004). No differences were found in terms of positive surgical margins. Finally, multivariable analyses predicting the risk of haemorrhagic complications found the off-clamp approach and shorter ischemia intervals associated with increased blood losses and risk of transfusion.

Although this study adds to a body of literature, reported results should be interpreted with caution, as they were probably influenced by eras of expertise by the surgeons involved. Indeed, off-clamp technique was used mostly during open surgery cases. Moreover, the reader should note that the time span considered went all the way back to 1988. It is renown that higher blood losses and transfusion rates typically decree the victory of robotics in the duel open versus robotic surgery. Taking this into account, given the high risk of bias, we believe that the approach to the renal hilum remains something to be based on surgeon’s preference and expertise.



[1] https://uroweb.org/guidelines/renal-cell-carcinoma/chapter/disease-management

[2] Pecoraro A, et al. Estimating Postoperative Renal Function After Surgery for Nonmetastatic Renal Masses: A Systematic Review of Available Prediction Models. Eur Urol Oncol. 2023 Apr;6(2):137-147. doi: 10.1016/j.euo.2022.11.007. Epub 2023 Jan 9.

[3] Campbell SC, et al. Every decade counts: a narrative review of functional recovery after partial nephrectomy. BJU Int 2022; 131: 165–72.

[4] Bertolo R, et al. Randomized trials to determine the ideal management of the renal artery during partial nephrectomy: Life’s under no obligation to give us what we expect. Int J Urol. 2022 Jan;29(1):92-93. doi: 10.1111/iju.14707. Epub 2021 Oct 7.

[5] Porpiglia F, et al. Long-term functional evaluation of the treated kidney in a prospective series of patients who underwent laparoscopic partial nephrectomy for small renal tumors. Eur Urol 2012; 62: 130–5.