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Article of the Week: Impact of warm ischaemia time on postoperative renal function after partial nephrectomy for clinical T1 renal cell carcinoma

Every Week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Impact of warm ischaemia time on postoperative renal function after partial nephrectomy for clinical T1 renal cell carcinoma: a propensity score-matched study

Hakmin Lee*, Byung D. Song*, Seok-Soo Byun*, Sang E. Lee* and Sung K. Hong*
*Department of Urology, Seoul National University Bundang Hospital, Seongnam, and Department of Urology, Seoul National University College of Medicine, Seoul, Korea

 

Objectives

To analyse the effect of prolonged warm ischaemia time (WIT) on long-term renal function after partial nephrectomy (PN), as controversy still exists as to whether prolonged WIT adversely affects the incidence of chronic kidney disease (CKD) after PN.

Patients and Methods

We reviewed data from 1816 patients who underwent PN for a clinical T1 renal tumour. The propensity scores for prolonged WIT were calculated with the shorter WIT group (<30 min) matched to the longer WIT group (≥30 min) in a 2:1 ratio. Multivariate analysis was used to determine independent predictors for occurrence of postoperative CKD [defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2] and major renal function deterioration (MRFD; defined as an eGFR decrease of ≥25% postoperatively).

Results

After propensity score matching, there was no significant difference in CKD-free survival between the two WIT groups (P = 0.787). Furthermore, longer WIT did not show any significant associations with postoperative CKD-free survival [hazard ratio (HR) 1.002, 95% confidence interval (CI) 0.989–1.015; P = 0.765) and MRFD-free survival (HR 1.014, 95% CI 1.000–1.028; P = 0.055). From further subgroup analyses using more specific WIT thresholds (≤20, 21–30, 31–40, 41–50, ≥50 min) and status of preoperative CKD, no significant differences were noted in CKD and MRFD-free survival amongst the subgroups (all P > 0.05).

Conclusions

Prolonged WIT was not associated with increased incidence of CKD or MRFD after PN.

Editorial: Impact of warm ischaemia time during partial nephrectomy on renal function – is it really a matter of time?

In the latest edition of the BJUI, Lee et al. [1] have revisited the question of defining the ideal limit of warm ischaemia time (WIT) and its impact on postoperative renal function in patients undergoing partial nephrectomy (PN).

Partial nephrectomy has replaced radical nephrectomy as the preferred treatment for T1 renal masses. This publication challenges the theory that ischaemic nephropathy is inevitable if the renal vessels are clamped beyond 30 min, leading to a long-term decline in renal function.

The authors in this series are to be commended for analysing a prospectively collected database on 1 816 patients in two institutions who underwent PN for clinical T1 renal tumours. Their primary endpoint was to investigate the impact of prolonged WIT on long-term renal function focusing on two clinical endpoints; chronic kidney disease, as estimated by an estimated GFR of <60 mL/min/1.73 m2, and major renal function deterioration defined as an increase in creatinine of >25% of the preoperative value.

Warm ischaemia time using a threshold of 30 min created two comparative groups. Patients were followed for up to 40 months after surgery. In addition to this, patients were further sub-stratified into five subgroups, critiquing the effect of WIT up to 50 min. A key feature of this paper [1] is the use of propensity score matching to adjust for any potential preoperative confounders affecting postoperative renal function, a technique also allowing matching of the two groups.

The authors correctly emphasise the direct relationship between tumour size and duration of WIT, with larger tumours requiring excision of more renal parenchyma and adding to ‘on-clamp’ time. Tumour size and renal function are vital determinants of suitability for PN [2]. This publication [1] clearly demonstrates that although large tumour size equated with prolonged clamp time, this was not the sole determinant of impaired long-term renal function.

The importance of other independent variables such as preoperative renal function, patient age and preserved renal parenchyma have been highlighted here as potentially playing a greater role than was previously appreciated.

The second and possibly more remarkable finding from this paper is that ischaemic time was not an independent predictor of ultimate renal function after PN. This contrasts with most other reports to date. Although not recommending using a WIT of up to 50 min, the results here suggest this may not be relevant to future renal function. It appears that long-term renal function after PN is primarily determined by the quantity and quality of renal parenchyma preserved, although the type and duration of ischaemia remain the most important modifiable factors, and warrant further evaluation [3].

When discussing this topic, it is interesting to refer to the initial bench work on this issue. The current approach to WIT is extrapolated from data derived from the histological changes occurring in nephrons during operative stone cases. From the data presented in this and other studies, it seems more relevant than ever to conduct clinical trials to assess this appropriately. Traditionally the time threshold for WIT is taken as 30 min, an arbitrarily placed time-point based on the above laboratory data. Beyond this value in the setting of room temperature renal ischaemia creates an array of injury centred on cellular adaptations beginning ~20 min after clamping and persisting beyond 60 min. This indicates that the traditional 30-min limit of WIT is a somewhat subjective time point and was not based on clinical outcomes.

Previous evidence suggests a 5% increase in risk for acute renal failure for every additional minute of WIT [4]. It is hard to ignore such data in exchange for this a contemporary study when so much is at stake for patient longevity. Advocators of zero-ischaemia PN have shown that those who benefit most from a zero-ischaemia technique are those with the poorest baseline renal function [5]. Most of these studies have shown that the renal functional outcomes are either equivalent or superior in zero-ischaemia cases involving small renal tumours [6].

On balance, the authors are to be credited with tackling such a controversial matter and highlighting the lack of good quality laboratory data. Clearly, factors other than WIT contribute to postoperative renal function but for now we must conclude that every minute ‘on-clamp’ does count.

Eva M. Bolton and Thomas H. Lynch
St. Jamess Hospital, Dublin, Ireland

References

1 Lee H, Song BD, Byun SS, Lee SE, Hong SK. Impact of warm ischaemia time on postoperative renal function after partial nephrectomy for clinical T1 renal cell carcinoma: a propensity score-matched study. BJU Int 2018; 121: 4652

 

2 Volpe A, Blute ML, Ficarra V et al. Renal ischemia and function after partial nephrectomy: a collaborative review of the literature. Eur Urol 2015; 68: 6174

 

3 Lane BR, Russo P, Uzzo RG et al. Comparison of cold and warm ischemia during partial nephrectomy in 660 solitary kidneys reveals predominant role of nonmodiable factors in determining ultimate renal function. J Urol 2011; 185: 4217

 

4 Thompson RH, Lane BR, Lohse CM et al. Every minute counts when the renal hilum is clamped during partial nephrectomy. Eur Urol 2010;58: 3405

 

 
6 Salami SS, George AK, Rais-Bahrami S, Okhunov Z, Waingankar NKavoussi LR. Off-clamp laparoscopic partial nephrectomy for hilar tumors: oncologic and renal functional outcomes. J Endourol 2014; 28: 1915

 

Article of the Week: NSS Across a Nation

Every Week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Archie Fernando and Tim O’Brien, discussing their paper.

If you only have time to read one article this week, it should be this one.

Nephron-sparing surgery across a nation – outcomes from the British Association of Urological Surgeons 2012 national partial nephrectomy audit

Archie Fernando*, Sarah Fowler* and Tim OBrien*, on behalf of the British
Association of Urological Surgeons (BAUS) 

 

*BAUS, The Royal College of Surgeons of England, and The Urology Centre, Guys and St Thomas NHS Foundation Trust, London, UK

 

BAUS-2012-national-partial-nephrectomy-audit-infographic-clipped

 

Click on image for full size infographic

 

Objective

To determine the scope and outcomes of nephron-sparing surgery (NSS), i.e. partial nephrectomy, across the UK and in so doing set a realistic benchmark and identify fresh contemporary challenges in NSS.

Patients and Methods

In 2012 reporting of outcomes of all types of nephrectomy became mandatory in the UK. In all, 148 surgeons in 86 centres prospectively entered data on 6 042 nephrectomies undertaken in 2012. This study is a retrospective analysis of the NSS procedures in the dataset.

Results

A total of 1 044 NSS procedures were recorded and the median (range) surgical volume was 4 (1–39) per consultant and 8 (1–59) per centre. In all, 36 surgeons and 10 centres reported on only one NSS. The indications for NSS were: elective with a tumour of ≤4.5 cm in 59%, elective with a tumour of >4.5 cm in 10%, relative in 7%, imperative in 12%, Von Hippel–Lindau in 1%, and unknown in 11%. The median (range) tumour size was 3.4 (0.8–30) cm. The technique used was minimally invasive surgery in 42%, open in 58%, with conversions in 4%. The histology results were: malignant in 80%, benign in 18%, and unknown in 2%. In patients aged <40 years 36% (36/101) had benign histology vs 17% (151/874) of those aged ≥40 years (P < 0.01). In patients with tumours of <2.5 cm 29% (69/238) had benign histology vs 14% (57/410) with tumours of 2.5–4 cm vs 8% (16/194) with tumours of ≥4 cm (P = 0.02). In patients aged <40 years with of tumours of <2.5 cm 44% (15/34) were benign. The 30-day mortality was 0.1% (1/1 044). There were major complications (Clavien–Dindo grade of ≥IIIa) in 5% (53/1 044). There was an increased risk of complications after extended elective NSS of 19% (19/101) vs elective at 12% (76/621) (relative risk [RR] 1.54; P < 0.01). Margins were recorded in 68% (709/1 044) of the patients, with positive margins identified in 7% (51/709). Positive surgical margins after NSS for pathological T3 (pT3) tumours were found in 47.8% (11/23) vs 6.1% (32/523) for pT1a, tumours (RR 5.61; P < 0.01). In all, 14% (894/6 042) of the patients underwent surgery for T1a tumours: 55% (488/894) by NSS, 42% (377/894) by radical nephrectomy (RN), and in 3% (29/894) the procedure used was unknown. Major complications after occurred in 4.9% (24/488) of NSS vs 1.3% (5/377) of RN (P < 0.01). Limitations included poor reporting of renal function data and no data on tumour complexity.

Conclusions

In its first year, mandatory national reporting has provided several challenging contemporary insights into NSS.

Editorial: SRMs – Where is the Wisdom We Have Lost in Knowledge?

The perceived wisdom that a small enhancing mass in the kidney represents a surgical lesion that automatically requires excision without the need for a preoperative biopsy has been challenged by Fernando et al. [1] in this issue of BJUI.

The authors are to be congratulated in bringing these data to publication to provoke debate on the treatment paradigm for small renal masses (SRMs) by reviewing nationally collected data on the main therapeutic surgical option: nephron-sparing surgery. As anyone who has attended a renal multidisciplinary meeting can testify, the predominant presentation of renal cancer is the incidentally detected SRM, often in elderly patients with significant comorbidity.

As the authors emphasize, these data are unique in representing a national picture encompassing both high- and low-volume centres, as opposed to the majority of the studies in the literature, which report data from high-volume tertiary referral centres.

Drawing conclusions from data requires a clear understanding of the source and quality. Most importantly, as these data only refer to patients undergoing nephron-sparing surgery, we need to be cautious about extrapolating to infer information on the management of SRMs in general.

For instance, a striking finding of the present study is the high incidence of benign lesions in the younger age groups. We have no knowledge of the numbers of patients with SRMs within the study period who had biopsy-proven benign disease and thus avoided surgery. It is probable that the true incidence of benign disease would be even higher if these cases had been recorded and included in the analysis.

An inherent difficulty with self-reported data is the issue of compliance, and this is clearly evident in the present study, with, for example, almost a third of cases missing data on surgical margin results. It would perhaps be helpful for future audits if the BAUS dataset had a clear definition of positive surgical margin in recognition of the surgical drift to enucleation rather than excision with a margin of renal parenchyma.

The variation in caseload between reporting centres raises important questions, as does the finding that two fifths of patients with T1a tumours underwent radical nephrectomies. As the authors concede, with the numbers involved and the absence of any measure of tumour complexity, it is difficult to draw firm conclusions; however, the study does highlight the need to examine this issue in future analyses and to consider including some form of renal scoring system in future audits.

Where do we go from here and what can we do with this information? First, we need to rethink our discussion with patients with SRMs. Can we justify performing major surgery with a one in 20 chance of a significant complication for a possible benign lesion without at least a pragmatic discussion of the role of renal biopsy with the patient? Indeed, one may argue, could it really be an ‘informed’ decision without it?

Second, we need to improve the quality of the data by encouraging robust data reporting, increasing the completion rate and considering adding data fields which will allow us to draw clearer conclusions on surgical margin and surgical outcome and volume relationships.

Third, we need to recognize that nephron-sparing surgery is only one component of the management of SRMs, which represents a major contemporary challenge in terms of health resources and, most importantly, in deciding the best treatment paradigm for our patients. If BAUS can carry out this audit, could we not extend this to all patients with SRMs, whether they have surgery, ablation or surveillance, and establish greater clarity on these treatment methods?

Michael Aitchison, Consultant Urological Surgeon and Maxine Tran, Senior Lecturer in Renal Cancer Surgery and Honorary Consultant Urological Surgeon

 

Renal Cancer Service, Royal Free NHS Foundation Trust, London, UK

 

Reference

 

Video: Nephron-Sparing Surgery Across the UK

Nephron-sparing surgery across a nation – outcomes from the British Association of Urological Surgeons 2012 national partial nephrectomy audit

Archie Fernando*, Sarah Fowler* and Tim OBrien*, on behalf of the British
Association of Urological Surgeons (BAUS) 

 

*BAUS, The Royal College of Surgeons of England, and The Urology Centre, Guys and St Thomas NHS Foundation Trust, London, UK

 

Objective

To determine the scope and outcomes of nephron-sparing surgery (NSS), i.e. partial nephrectomy, across the UK and in so doing set a realistic benchmark and identify fresh contemporary challenges in NSS.

Patients and Methods

In 2012 reporting of outcomes of all types of nephrectomy became mandatory in the UK. In all, 148 surgeons in 86 centres prospectively entered data on 6 042 nephrectomies undertaken in 2012. This study is a retrospective analysis of the NSS procedures in the dataset.

Jun AOTW Results Image 4

Results

A total of 1 044 NSS procedures were recorded and the median (range) surgical volume was 4 (1–39) per consultant and 8 (1–59) per centre. In all, 36 surgeons and 10 centres reported on only one NSS. The indications for NSS were: elective with a tumour of ≤4.5 cm in 59%, elective with a tumour of >4.5 cm in 10%, relative in 7%, imperative in 12%, Von Hippel–Lindau in 1%, and unknown in 11%. The median (range) tumour size was 3.4 (0.8–30) cm. The technique used was minimally invasive surgery in 42%, open in 58%, with conversions in 4%. The histology results were: malignant in 80%, benign in 18%, and unknown in 2%. In patients aged <40 years 36% (36/101) had benign histology vs 17% (151/874) of those aged ≥40 years (P < 0.01). In patients with tumours of <2.5 cm 29% (69/238) had benign histology vs 14% (57/410) with tumours of 2.5–4 cm vs 8% (16/194) with tumours of ≥4 cm (P = 0.02). In patients aged <40 years with of tumours of <2.5 cm 44% (15/34) were benign. The 30-day mortality was 0.1% (1/1 044). There were major complications (Clavien–Dindo grade of ≥IIIa) in 5% (53/1 044). There was an increased risk of complications after extended elective NSS of 19% (19/101) vs elective at 12% (76/621) (relative risk [RR] 1.54; P < 0.01). Margins were recorded in 68% (709/1 044) of the patients, with positive margins identified in 7% (51/709). Positive surgical margins after NSS for pathological T3 (pT3) tumours were found in 47.8% (11/23) vs 6.1% (32/523) for pT1a, tumours (RR 5.61; P < 0.01). In all, 14% (894/6 042) of the patients underwent surgery for T1a tumours: 55% (488/894) by NSS, 42% (377/894) by radical nephrectomy (RN), and in 3% (29/894) the procedure used was unknown. Major complications after occurred in 4.9% (24/488) of NSS vs 1.3% (5/377) of RN (P < 0.01). Limitations included poor reporting of renal function data and no data on tumour complexity.

Conclusions

In its first year, mandatory national reporting has provided several challenging contemporary insights into NSS.

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