Tag Archive for: chronic kidney disease

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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: Identifying predictors of renal function decline after surgery

Every week the Editor-in-Chief selects the 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.

Preoperative predictors of renal function decline after radical nephroureterectomy for upper tract urothelial carcinoma

Matthew Kaag, Landon Trost*, R. Houston Thompson*, Ricardo Favaretto†, Vanessa Elliott, Shahrokh F. Shariat‡, Alexandra Maschino†, Emily Vertosick†, Jay D. Raman and Guido Dalbagni†

Penn State Hershey Medical Center, Hershey, PA, *Mayo Clinic, Rochester, MN, †Memorial Sloan-Kettering Cancer Center, New York, NY, USA, and ‡Medical University of Vienna, Vienna, Austria

Read the full article
OBJECTIVES

To model renal function after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). To identify predictors of renal function decline after surgery, thereby allowing the identification of patients likely to be ineligible for cisplatin-based chemotherapy in the adjuvant setting.

PATIENTS AND METHODS

We retrospectively identified 374 patients treated with RNU for UTUC at three centres between 1995 and 2010. Estimated glomerular filtration rate (eGFR) was calculated using Chronic Kidney Disease Epidemiology Collaboration equation before RNU and at early (1–5 months after RNU) and late (>5 months) time points after RNU. Only patients deemed eligible for cisplatin-based chemotherapy before RNU (preoperative glomerular filtration rate [GFR] ≥60 mL/min/1.73 m2) were included. Multivariable analysis identified the preoperative predictors of eGFR after RNU at early postoperative and late postoperative time points.

RESULTS
A total of 163 patients had an eligible early post-RNU eGFR measurement and 172 had an eligible late eGFR measurement. The median eGFR declined by 32% and did not show a significant trend toward recovery over time (P = 0.4). On multivariable analysis preoperative eGFR and patient age were significantly associated with early and late postoperative eGFR, while Charlson comorbidity index score was significantly associated with late postoperative eGFR alone.
 

CONCLUSIONS
In patients with normal preoperative eGFR (≥60 mL/min/1.73 m2), renal function decreases by one-third after RNU and does not show evidence of recovery over time. Elderly patients and those with pre-RNU eGFR closer to 60 mL/min/1.73 m2 (lower eGFR in the present cohort) are more likely to be ineligible for adjuvant cisplatin-based chemotherapy regimens because of renal function loss after RNU.

 

 

Editorial: ‘Discontent is the first necessity of progress’, Thomas A. Edison

This study from Kaag et al. [1] investigates predictors of renal functional decline after radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC). They evaluate early (2 months) and late (6 months) predictors of renal functional decline, finding that on a multivariable model only age at surgery and preoperative renal function were independently associated with early postoperative function. This is an intuitive finding whereby we expect older patients and those with lower renal function to have a more dramatic decrease in renal function after RNU.

Age, preoperative renal function, and Charlson score were associated with late functional recovery. The latter is a counterintuitive finding, as higher Charlson score was associated with less decrease in renal function. Charlson comorbidity was not significant on univariate analyses. Why it would become significant on multivariate is unclear. Whether it is an artifact related to study methodology or is a real phenomenon will require further study.

Unquestionably, this study [1] adds to the growing discontent of our current management of UTUC. The authors cogently discuss the issues related to better risk stratification as a natural consequence of instituting a neoadjuvant chemotherapy paradigm in those with high-risk disease. Multiple retrospective studies have failed to show a benefit of adjuvant chemotherapy, whereas now we have a matched-cohort study showing significant rates of downstaging and complete remission [2], and as well significantly improved 5-year survival, with institution of a neoadjuvant paradigm [3]. One cannot view the dismal outcomes of this disease without being discontent and wishing for progress. We need to continue getting out the message to not only urologists who reflexively institute RNU in patients with a risk-unstratified upper tract filling defect, but as well many medical oncologists who can only function based on guidance from level I data, which for this disease, will be a long time coming.

Read the full article

Surena F. Matin

Department of Urology, MD Anderson Cancer Center, Houston, TX, USA

References

1 Kaag M, Trost L, Thompson RH et al. Pre-operative predictors of renal function decline following radical nephroureterectomy for upper tract urothelial carcinoma. BJU Int 2014; 114: 674–9

2 Matin SF, Margulis V, Kamat A et al. Incidence of downstaging and complete remission after neoadjuvant chemotherapy for high-risk upper tract transitional cell carcinoma. Cancer 2010; 116: 3127–34

3 Porten S, Siefker-Radtke AO, Xiao L et al. Neoadjuvant chemotherapy improves survival of patients with upper tract urothelial carcinoma. Cancer 2014; 120: 1794–9

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