European Urology

1. The challenge of preserving renal function

Partial nephrectomy (PN) has gained popularity due to the increased incidence of small incidental renal tumours and the procedure's excellent oncologic results; however, current scientific evidence suggests that preservation of renal function should be given priority. Go and al [1] showed an independent, graded association between reduced estimated glomerular filtration rate (GFR) and the risks of cardiovascular events, hospitalisation, and death from any cause in a large community-based population. Radical nephrectomy is now understood as a risk factor for chronic kidney disease, which in turn increases the risk of cardiovascular events and all-cause mortality. Huang et al [2] demonstrated in 662 patient-candidates for radical nephrectomy or PN that 26% had a certain degree of impaired renal function at baseline. This study also highlighted that the risk of new onset of chronic kidney disease was significantly increased in patients undergoing radical nephrectomy versus PN. Four recent series have confirmed that patients treated with radical nephrectomy are at increased risk of non–cancer-related death when compared with those being treated with PN. Specifically, Weight et al [3] demonstrated that in patients with T1b tumours, the average excess loss of renal function observed with radical nephrectomy was associated with a 25% increased risk of cardiac death and a 17% increased risk of death from any cause.

These accumulated data should prompt us to choose options that are less deleterious to renal function when determining treatment for small renal tumours. It is obvious that a certain number of small renal tumours are indolent and not life threatening; therefore, we should integrate information such as age, comorbidities, baseline renal function, tumour biopsy results, and technical difficulty of PN into our decision-taking algorithm.

2. Widening indications of partial nephrectomy: Oncologic outcome is not the only issue

The 4-cm cut-off has long been the upper limit of indication for elective PN. The validity of 4 cm as a threshold for nephron-sparing surgery was subsequently questioned. During that period, intensive debates centred on legitimate oncologic issues, and renal function outcome was no longer the main focus. Several series have confirmed similar oncologic outcomes for appropriately selected patients with T1b renal tumours treated with either radical nephrectomy or elective PN [4].

Our group demonstrated that pushing PN indications translated into slightly increased but acceptable morbidity. Interestingly, in our study, ischaemic times did not significantly differ in tumours <4 cm and >4 cm [5]. Recently, we finally demonstrated that the benefit for renal function offered by nephron-sparing surgery over radical nephrectomy persisted, even when expanding nephron-sparing surgery indications beyond the traditional 4-cm cut-off [6].

3. Prolonged warm ischaemia time during laparoscopic partial nephrectomy: Is it still an issue?

The emergence of laparoscopic PN (LPN) prompts investigators to revisit the impact of warm renal ischaemia on renal function. The safe duration of warm ischaemia remains controversial. Experimental studies on human kidneys demonstrated that renal damage and cellular degeneration of the nephron begin after 20–30 min of clamping. Warm ischaemia time (WIT), as emphasised recently by an international expert panel [7], is the strongest modifiable surgical risk factor for postoperative chronic kidney disease. The experts recommended that WIT should be kept to <20 minutes and that in difficult cases cold ischaemia should be started immediately but should not exceed 35 min. Although renal function after laparoscopic or open procedures seems to be equivalent in series from high-volume laparoscopic centres, most initial large laparoscopic series had WIT of about 30 min. Methods of surface cooling (ice slush) have also been developed for LPN, along with intra-arterial cooling perfusion techniques. These techniques are logistically difficult to implement, and it is not proven that an appropriately low renal parenchyma temperature is reached. However, the early unclamping technique has recently been introduced and allows significant shortening of WIT to the cut-off of <20 min [8]. The main limitation of such a favourable trend is that it is inseparable from both required advanced laparoscopic skills and high-volume patient recruitment.

Robotic PN (RPN) represents a promising alternative procedure that potentially combines the advantages of open and laparoscopic procedures. Early results suggest that WIT from RPN is close to that of open PN (OPN; approximately 20 min). Additionally, the learning curve seems to be shorter for RPN than for LPN [9].

It is still the case that technically feasible surgery is not necessarily desirable for the patient. Oncologic goals, renal function, and surgical risks must be balanced. This is particularly true because alternative options exist for the management of small renal tumours, including active surveillance or ablative techniques that are not likely to be dangerous for renal function.

4. Solitary kidney as a model for assessing warm ischaemic damage during partial nephrectomy

Ischaemic damage to a renal unit during elective PN is potentially masked by the compensatory role of the normal contralateral kidney. Therefore, analysing the renal function of solitary kidney is particularly informative with regard to the consequences of various technical scenarios during PN. This approach is useful not only for appropriate surgical management of patients with solitary kidney but also for understanding the consequences of ischaemia when performing elective PN.

In this issue of European Urology, Thompson et al [10] retrospectively compared short- and long-term renal effects of warm ischaemia versus no ischaemia in solitary-kidney patients treated with PN. This study is an update with more accurate assessment of renal function from a previous series comparing different OPN techniques including no ischaemia, warm ischaemia, and cold ischaemia through a large multi-institutional study. The authors concluded that whenever pedicle clamping was expected, warm ischaemia should be completed within 20 min and cold ischaemia should be completed within 35 min. These previous data were fully consistent with the results from Lane et al [11] showing that LPN for tumour in solitary kidney was associated with longer mean WIT, higher proportion of warm ischaemia >20 min, higher proportion of postsurgery dialysis, and higher risk of postoperative complications. The authors concluded that OPN should be preferred in the imperative setting.

In the present study, Thompson et al [10] show that warm ischaemia patients are significantly more likely to develop acute renal failure in the postoperative period and new-onset stage 4 chronic kidney disease during follow-up compared with patients managed without hilar clamping. The authors logically proposed that PN with no clamping should be used whenever technically feasible, especially in patients with solitary kidney.

The strength of this study is that it was performed in a large series of patients with solitary kidneys (n = 458) [10], whereas the vast majority of prior studies assessing the impact of ischaemia included patients with a normal contralateral kidney. No ischaemia was used in 96 patients (21%), whereas 362 patients (79%) had a median WIT of 21 min. Warm ischaemia patients were significantly more likely to develop acute renal failure (hazard ratio [HR]: 2.1) and new onset of stage 4 chronic kidney disease (HR: 2.3) during a mean follow-up of 3.3 yr. Although patients treated with warm ischaemia had a significantly higher preoperative GFR and larger tumours, similar results were obtained with multivariable analysis after adjusting for preoperative GFR, tumour size, and type of PN. Notably, the absence of renal vessel clamping did not result in increased morbidity, especially with regard to pre- and postoperative bleeding. This result could be explained by significantly more exophytic and small tumours in the no-ischaemia group. Therefore, these morbidity results do not necessarily translate to more complex imperative settings where clamping is necessary to allow for good haemostasis, accurate surgical collecting system closure, and achievement of negative surgical margins. In the current study, positive margin rates in patients with or without clamping did not differ significantly, but caution must again be taken with interpretation because more favourable clinical features were present in the nonclamping group.

5. What is the best partial nephrectomy technique?

Tumour size is no longer a limiting factor for PN [4]. In addition to oncologic and surgical outcomes that are now well managed, post-PN renal function is increasingly becoming a major hallmark of quality. In this respect, ischaemia time is the key point. As shown by Thompson et al [10], the least deleterious surgical approach for PN with regard to renal function is PN without ischaemia. If ischaemia is required, it should be kept to the shortest duration possible, ideally <20 min. These goals can be reached with laparoscopy to preserve the advantages of a minimally invasive surgical approach; however, prolonged learning curve, extensive experience, and advanced laparoscopic skills limit the safe use of this technique. RPN currently appears to be an attractive option for combining the advantages of laparoscopy and short ischaemic duration. Ultimately, the best PN technique combines good oncologic control, reproducible short ischaemia time, and good postoperative quality of life for patients with the skills of a particular surgeon.

Conflicts of interest

The authors have nothing to disclose.