EURURO-6067; No. of Pages 14 EUROPEAN UROLOGY XXX (2015) XXX–XXX
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Platinum Priority – Review – Kidney Cancer Editorial by XXX on pp. x–y of this issue
Renal Ischemia and Function After Partial Nephrectomy: A Collaborative Review of the Literature Alessandro Volpe a,*, Michael L. Blute b, Vincenzo Ficarra c, Inderbir S. Gill d, Alexander Kutikov e, Francesco Porpiglia f, Craig Rogers g, Karim A. Touijer h, Hendrik Van Poppel i, R. Houston Thompson j a
Division of Urology, Department of Translational Medicine, University of Eastern Piedmont, Maggiore della Carita` Hospital, Novara, Italy; b Department of
Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; c Division of Urology, Department of Experimental and Clinical Medical Sciences, University of Udine, Italy; d Catherine and Joseph Aresty Department of Urology, USC Institute of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; e Division of Urologic Oncology, Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA; f
Division of Urology, Department of Oncology, University of Turin, San Luigi Hospital, Orbassano, Turin, Italy;
g
Vattikuti Urology Institute, Henry Ford
Hospital, Detroit, MI, USA; h Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; i Department of Urology, Leuven Cancer Institute, Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium; j Department of Urology, Mayo Clinic, Rochester, MN, USA
Article info
Abstract
Article history: Accepted January 26, 2015
Context: Partial nephrectomy (PN) is the current gold standard treatment for small localized renal tumors.; however, the impact of duration and type of intraoperative ischemia on renal function (RF) after PN is a subject of significant debate. Objective: To review the current evidence on the relationship of intraoperative ischemia and RF after PN. Evidence acquisition: A review of English-language publications on renal ischemia and RF after PN was performed from 2005 to 2014 using the Medline, Embase, and Web of Science databases. Ninety-one articles were selected with the consensus of all authors and analyzed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Evidence synthesis: The vast majority of reviewed studies were retrospective, nonrandomized observations. Based on the current literature, RF recovery after PN is strongly associated with preoperative RF and the amount of healthy kidney parenchyma preserved. Warm ischemia time (WIT) is modifiable and prolonged warm ischemia is significantly associated with adverse postoperative RF. Available data suggest a benefit of keeping WIT 35 min were associated
with a higher incidence of ARF (p = 0.002 and p = 0.003, respectively). In addition, WIT >20 min was associated with an increased risk of CKD (41% vs. 19%; p = 0.008), increase in sCr >0.5 mg/dl (42% vs 15%; p < 0.001), and permanent dialysis (10% vs 4%; p = 0.145) [33]. Three years later, further observations from the same institutions focused the analysis on 362 patients who underwent OPN or LPN using warm ischemia with hilar clamping (median: 21 min) in solitary kidneys. A strength of this study is that RF was assessed not only by sCr values but also with eGFR using the MDRD equation. Longer WIT as a continuous variable was associated with ARF (odds ratio [OR]: 1.05 for each 1-min increase; p < 0.001), eGFR 25 min remained significantly associated with new-onset stage 4 CKD in a multivariate analysis adjusting for the parenchymal quantity and quality factors (HR: 2.27; p = 0.049). Collectively, these results, presented in Table 1, suggest that preoperative RF, amount of healthy parenchyma after PN, and WIT (continuous variable) are each associated with short-term RF following hilar clamping. In addition, long-term RF is dependent on preoperative RF, amount of healthy parenchyma preserved, and minimizing WIT to 20 min and CIT >35 min were associated with a higher incidence of acute renal failure. WIT >20 min was associated with an increased risk of chronic renal failure and permanent dialysis. Longer WIT was associated with acute renal failure, a GFR 25–30 min [38–40]. Preoperative RF and amount of preserved renal parenchyma were factored in the analysis in some but not all of these studies (Table 2). Chan et al [41] included the intraoperative visually estimated functioning residual renal volume after PN in the analysis of postoperative RF of the operated kidney, using 99m Tc-MAG-3 scintigraphy. The authors observed that this variable was the most accurate predictor of unilateral RF 1 mo after surgery at univariable analysis [41]. Song et al also observed that the percent of residual renal parenchyma evaluated by postoperative computed tomography (CT) scan was an independent predictor of eGFR at a median of 6.5 mo from surgery in elective cases of PN with bilateral kidneys [42]. Finally, Porpiglia et al [43] recently reported the longterm outcomes of a series of 54 LPNs in patients with bilateral renal units. The split function of the affected kidneys at 99mTc-MAG-3 scintigraphy decreased significantly at 3 mo after surgery and subsequently remained stable after a minimum follow-up of 4 yr. Age and WIT were significant predictors of loss of function of the operated
kidney at 3 mo, whereas only WIT was a significant predictor at 48 mo [43]. 3.2.6.
Human studies evaluating techniques of early unclamping, no
ischemia, or selective ischemia
Several technical modifications have been proposed to reduce or minimize WIT [44,45]. These concepts can be applied to all surgical approaches but have been more intensively pursued by laparoscopic surgeons due to the average longer WIT reported with this approach for its intrinsic technical challenges [46]. The early unclamping technique implies clamping of the renal hilum only for the duration of tumor excision and placement of the initial central running suture on the renal medulla. All subsequent suturing in the PN bed to ensure parenchymal hemostasis and pelvicaliceal repair is done in the perfused revascularized kidney. Gill et al reported that this technical modification allowed a significantly shorter WIT (14.4 vs 31.9 and 31.6 min in previous periods of experience; p < 0.0001), which resulted in significantly superior RF outcomes (decrease in eGFR within 90 postoperative days: 11% vs 18% and 20%, respectively; p < 0.0001) [47]. The attempt to decrease intraoperative WIT has also led to the introduction of the concept of off-clamp PN and of PN with selective clamping, which aims to avoid or minimize the ischemic injury on the healthy parenchyma of the operated kidneys (Table 3). Thompson et al [48] retrospectively compared the shortand long-term RF outcomes of 362 patients who underwent OPN or LPN in a solitary kidney with clamping of the renal artery (median: 21 min) with those of 96 patients who had no intraoperative renal ischemia. The authors observed that the warm ischemia group had significantly increased risk of acute kidney injury after surgery and increased risk of newonset CKD during follow-up [48]. A similar analysis on a cohort of patients with bilateral kidneys showed a higher rate of long-term CKD in patients after PN performed with WIT versus no ischemia (24.4% vs 12.5%). Conversely, off-clamp cases had a higher estimated blood loss (EBL; median: 300 vs 200 ml) but similar complication rates [49]. It is important to note that a proportion of off-clamp cases in these and other reports were performed with simple manual compression of peritumoral parenchyma [48–50]. The application of Kauffman clamps on the kidney was also proposed to achieve hemostasis during tumor resection [51]. The perioperative and functional outcomes of off-clamp PN performed with robotic assistance were retrospectively assessed in a large multi-institutional series of 886 cases. In propensity score-matched analyses, the off-clamp patients had a significantly shorter mean operative time, a higher EBL, and a smaller decrease in eGFR compared with those with intraoperative ischemia (2% vs 6%; p = 0.008) [52]. More recently, Porpiglia et al [53] used renal scans to compare the postoperative RF after LPN with clamping of the renal artery 30 min and is only partially reversible. The functional impairment of the operated kidney is significantly worse with WIT >32 min. Preoperative RF and percent of functional volume preservation are the primary determinants of long-term functional outcomes in patients with normal preoperative RF who have ischemia time within acceptable limits. RF changes did not correlate with ischemia duration. Renal structural changes were much less severe than observed in animal models that used similar duration of ischemia. Acute kidney injury biomarkers were only mildly elevated and did not correlate with RF or ischemia duration. WIT did not have a clinically significant impact on global RF after LPN WIT and endophytic tumor location are associated with a statistically significant loss of differential RF, but only in the group who experienced a WIT >30 min. While total RF is almost unaffected after surgery, a WIT >25 min leads to a significant decrease in effective renal plasma flow on the operated side. WIT as a continuous variable is associated with greater loss of RF. ROC analysis identifies 25 min as a safe WIT cut off. Loss of RF occurs within 3 mo and remains stable until 12 mo after LPN. Intraoperative, visually estimated preserved parenchyma volume, radiologic tumor size, and procedure type significantly correlate with postoperative unilateral RF at univariable analysis. No factor is an independent predictor at multivariable analysis. Renal volume reduction, tumor location, and patient age are independent predictors of postoperative RF at multivariable analysis.
4
Mean: 3.4 1.8
* §
39
OPN/LPN
To assess a novel method to estimate the percent of functional volume preservation and to assess its effect on postoperative functional outcomes
Median CIT: 38.5 Median WIT: 24.5
Median: 3.5
40
OPN
To prospectively assess the renal response to clamp ischemia and reperfusion after PN, including histologic changes on biopsies performed before, during, and after clamping, and changes in biomarkers of acute kidney injury
Mean CIT: 48 Mean WIT: 32.3
Median: 4.1
401
LPN
Median WIT: 29
Median: 2.5
56
LPN
To assess the influence of renal ischemia on long-term global RF assessed with eGFR To evaluate the effect of WIT and other factors on differential RF of the operated kidney assessed by using renal scans (preoperative, 10 d postoperative)
Mean: 30 9
Mean: 3.2 1.6
**
32
OPN (n = 20) LPN (n = 2012)
OPN: 24.2 6.2 LPN: 24.5 7.2
OPN: 2.5 0.6 LPN: 2.9 1.1
* §
53
LPN
To evaluate the differential RF of the operated kidney by using renal scans (preoperative; 1 wk and 6 mo postoperative) To assess the effects of WIT on RF after LPN in patients with a normal contralateral kidney by using renal scans (preoperative; 3 and 6 mo postoperative)
Mean: 21.9
Mean: 3.0
65
OPN (n = 35) LPN (n = 30)
To retrospectively evaluate predictors of postoperative unilateral RF by using renal scans (preoperative, 1 mo postoperative)
OPN: 29.8 9.9 LPN: 28.7 11.2
OPN: 3.8 1.9 LPN: 2.6 1.1
117
OPN (n = 52) LPN (n = 65)
To investigate factors determining RF decrease. (preoperative; 6 mo postoperative)
LPN
To evaluate the long-term effects of WI on RF by using renal scans (preoperative; 3 and 6 mo postoperative; yearly)
OPN: 20.5 (range: 8–35) LPN: 33.5 (range: 13–75) Mean: 27.98 11.12
OPN: 3.72 (range: 0.9–11) LPN: 2.14 (range: 0.8–4) Mean: 3.69 1.39
Porpiglia et al [39]
§
Level of evidence
Mean: 39 8.1
Funahashi et al [40]
Song et al [42]
Main outcomes
To evaluate the impairment of RF of the operated kidney 12 mo after surgery by using renal scans (preoperative; 5 d, 3 mo, and 6 mo postoperative)
*
* §
Tumor size, cm
LPN with WIT >30 min
Shikanov et al [87]
Chan et al [41]
Ischemia time, min
18
Parekh et al [3]
Pouliot et al [38]
Aim of the study
§
Porpiglia et al [37]
Simmons et al [4]
Surgical approach
Porpiglia et al [44]
§
54
Split RF of the operated kidney decreases significantly at 3 mo from surgery and subsequently remains stable during follow-up up to 4 yr. WIT is the only independent predictor of split RF at 4 yr from surgery.
4
2
4 4
4
4
4
EUROPEAN UROLOGY XXX (2015) XXX–XXX
Please cite this article in press as: Volpe A, et al. Renal Ischemia and Function After Partial Nephrectomy: A Collaborative Review of the Literature. Eur Urol (2015), http://dx.doi.org/10.1016/j.eururo.2015.01.025
Table 2 – Recent studies on renal ischemia during partial nephrectomy in the setting of bilateral kidneys
4
4
CIT = cold ischemia time; eGFR = estimated glomerular filtration rate; LPN = laparoscopic partial nephrectomy; OPN = open partial nephrectomy; RF = renal function; WIT = warm ischemia time. Assessment of the amount of preserved/resected renal parenchyma was included in the analysis of predictors of postoperative renal functional outcomes. * Assessment of preoperative renal function was included in the analysis of predictors of postoperative renal functional outcomes. ** Analysis of predictors of postoperative renal functional outcomes not performed. §
7
Study
Patients, no.
Thompson et al [48]
**
Kopp et al [49]
Smith et al [50]
**
Ng et al [55]
**
**
Shao et al [58]
**
Ischemia time, min
OPN (n = 411) To compare the short- and long- Median: 21 (range: 4–55) LPN (n = 47) term renal effects of WI vs no ischemia in patients with a solitary kidney
Clamped PN (n = 164) Clampless PN (n = 64)
OPN
Clamped PN (n = 49) RAPN Clampless PN (n = 283)
Tumor size, cm
Nephrometry score (mean)
Mean: 3.4 Mean: 2.5
–
Mean: 24.5 0
Median: 3.5 Median: 4.0
6.9 1.5 6.4 1.5
Mean: 20 0
Median: 3.0 Median: 2.8
–
To evaluate the functional outcomes of RAPN with and without hilar clamping in a propensity score matched analysis To compare postoperative RF of clampless vs clamped LPN (WIT 30 min in 82.5% of the cases [3]. The authors showed greater-than-expected resistance to ischemia time of human kidneys, with little or no acute RF loss in the early postoperative period. Progressive levels of ischemia up to 61 min had no effect on the injury produced, which was assessed functionally by sCr and cystatin C levels, structurally by light and electron microscopy and immunofluorescence analysis, and by biomarkers excreted in the urine [3]. The strength of this prospective study is that pathologists who evaluated renal structure and biomarkers were blinded to the clinical results and the duration of ischemia. In contrast, the study is limited by the lack of follow-up beyond the hospital duration of a few days, by the presence of a mixed population of patients who underwent cold and warm ischemia, by the lack of information on tumor complexity and estimated volume of preserved parenchyma, and by the absence of RF scans to evaluate contributions from the contralateral kidney. At present, efforts should be always made to minimize ischemia time when planning surgery, especially with imperative indications. Based on level 3–4 evidence from several studies, 20–25 min represents the most accurate cut-off to separate patients who do and do not develop short- and long-term RF decline after PN [15,33,34,39,40, 64,65] (Tables 1 and 2). The temporal trend of loss of RF has been diffusely investigated, especially in the setting of bilateral kidneys. RF appears to decrease immediately after PN and to partially recover to reach a new steady state, generally within 3 wk to 3 mo after PN [39]. It was suggested that the longer the period of RF decline after PN, the worse the nadir and the ultimate GFR. However, RF appears to remain stable after 3 mo from surgery up to 4 yr, according to recent data [43]. The use of cold ischemia is variable and depends on the institution and surgeon. In general, cold ischemia has been used liberally in OPN for those cases where a longer clamping time was expected. Surface hypothermia is generally instituted immediately after vascular clamping and maintained for 10 min before commencing tumor resection [66]. Indeed, there is clear evidence of the protective role of renal cooling with respect to functional injury, with longer periods of cold ischemia harming the nephrons similarly to shorter periods of warm ischemia [5,67]. Yossepowitch et al [68] analyzed RF with eGFR in 592 OPNs with a median CIT of 35 min. At multivariable analysis, CIT was significantly associated with early postsurgical eGFR changes, but not with a significant eGFR decrease 12 mo after surgery [68]. According to Iida et al, a CIT
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Platinum Priority – Review – Kidney Cancer Editorial by XXX on pp. x–y of this issue
Renal Ischemia and Function After Partial Nephrectomy: A Collaborative Review of the Literature Alessandro Volpe a,*, Michael L. Blute b, Vincenzo Ficarra c, Inderbir S. Gill d, Alexander Kutikov e, Francesco Porpiglia f, Craig Rogers g, Karim A. Touijer h, Hendrik Van Poppel i, R. Houston Thompson j a
Division of Urology, Department of Translational Medicine, University of Eastern Piedmont, Maggiore della Carita` Hospital, Novara, Italy; b Department of
Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; c Division of Urology, Department of Experimental and Clinical Medical Sciences, University of Udine, Italy; d Catherine and Joseph Aresty Department of Urology, USC Institute of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; e Division of Urologic Oncology, Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA; f
Division of Urology, Department of Oncology, University of Turin, San Luigi Hospital, Orbassano, Turin, Italy;
g
Vattikuti Urology Institute, Henry Ford
Hospital, Detroit, MI, USA; h Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; i Department of Urology, Leuven Cancer Institute, Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium; j Department of Urology, Mayo Clinic, Rochester, MN, USA
Article info
Abstract
Article history: Accepted January 26, 2015
Context: Partial nephrectomy (PN) is the current gold standard treatment for small localized renal tumors.; however, the impact of duration and type of intraoperative ischemia on renal function (RF) after PN is a subject of significant debate. Objective: To review the current evidence on the relationship of intraoperative ischemia and RF after PN. Evidence acquisition: A review of English-language publications on renal ischemia and RF after PN was performed from 2005 to 2014 using the Medline, Embase, and Web of Science databases. Ninety-one articles were selected with the consensus of all authors and analyzed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Evidence synthesis: The vast majority of reviewed studies were retrospective, nonrandomized observations. Based on the current literature, RF recovery after PN is strongly associated with preoperative RF and the amount of healthy kidney parenchyma preserved. Warm ischemia time (WIT) is modifiable and prolonged warm ischemia is significantly associated with adverse postoperative RF. Available data suggest a benefit of keeping WIT 35 min were associated
with a higher incidence of ARF (p = 0.002 and p = 0.003, respectively). In addition, WIT >20 min was associated with an increased risk of CKD (41% vs. 19%; p = 0.008), increase in sCr >0.5 mg/dl (42% vs 15%; p < 0.001), and permanent dialysis (10% vs 4%; p = 0.145) [33]. Three years later, further observations from the same institutions focused the analysis on 362 patients who underwent OPN or LPN using warm ischemia with hilar clamping (median: 21 min) in solitary kidneys. A strength of this study is that RF was assessed not only by sCr values but also with eGFR using the MDRD equation. Longer WIT as a continuous variable was associated with ARF (odds ratio [OR]: 1.05 for each 1-min increase; p < 0.001), eGFR 25 min remained significantly associated with new-onset stage 4 CKD in a multivariate analysis adjusting for the parenchymal quantity and quality factors (HR: 2.27; p = 0.049). Collectively, these results, presented in Table 1, suggest that preoperative RF, amount of healthy parenchyma after PN, and WIT (continuous variable) are each associated with short-term RF following hilar clamping. In addition, long-term RF is dependent on preoperative RF, amount of healthy parenchyma preserved, and minimizing WIT to 20 min and CIT >35 min were associated with a higher incidence of acute renal failure. WIT >20 min was associated with an increased risk of chronic renal failure and permanent dialysis. Longer WIT was associated with acute renal failure, a GFR 25–30 min [38–40]. Preoperative RF and amount of preserved renal parenchyma were factored in the analysis in some but not all of these studies (Table 2). Chan et al [41] included the intraoperative visually estimated functioning residual renal volume after PN in the analysis of postoperative RF of the operated kidney, using 99m Tc-MAG-3 scintigraphy. The authors observed that this variable was the most accurate predictor of unilateral RF 1 mo after surgery at univariable analysis [41]. Song et al also observed that the percent of residual renal parenchyma evaluated by postoperative computed tomography (CT) scan was an independent predictor of eGFR at a median of 6.5 mo from surgery in elective cases of PN with bilateral kidneys [42]. Finally, Porpiglia et al [43] recently reported the longterm outcomes of a series of 54 LPNs in patients with bilateral renal units. The split function of the affected kidneys at 99mTc-MAG-3 scintigraphy decreased significantly at 3 mo after surgery and subsequently remained stable after a minimum follow-up of 4 yr. Age and WIT were significant predictors of loss of function of the operated
kidney at 3 mo, whereas only WIT was a significant predictor at 48 mo [43]. 3.2.6.
Human studies evaluating techniques of early unclamping, no
ischemia, or selective ischemia
Several technical modifications have been proposed to reduce or minimize WIT [44,45]. These concepts can be applied to all surgical approaches but have been more intensively pursued by laparoscopic surgeons due to the average longer WIT reported with this approach for its intrinsic technical challenges [46]. The early unclamping technique implies clamping of the renal hilum only for the duration of tumor excision and placement of the initial central running suture on the renal medulla. All subsequent suturing in the PN bed to ensure parenchymal hemostasis and pelvicaliceal repair is done in the perfused revascularized kidney. Gill et al reported that this technical modification allowed a significantly shorter WIT (14.4 vs 31.9 and 31.6 min in previous periods of experience; p < 0.0001), which resulted in significantly superior RF outcomes (decrease in eGFR within 90 postoperative days: 11% vs 18% and 20%, respectively; p < 0.0001) [47]. The attempt to decrease intraoperative WIT has also led to the introduction of the concept of off-clamp PN and of PN with selective clamping, which aims to avoid or minimize the ischemic injury on the healthy parenchyma of the operated kidneys (Table 3). Thompson et al [48] retrospectively compared the shortand long-term RF outcomes of 362 patients who underwent OPN or LPN in a solitary kidney with clamping of the renal artery (median: 21 min) with those of 96 patients who had no intraoperative renal ischemia. The authors observed that the warm ischemia group had significantly increased risk of acute kidney injury after surgery and increased risk of newonset CKD during follow-up [48]. A similar analysis on a cohort of patients with bilateral kidneys showed a higher rate of long-term CKD in patients after PN performed with WIT versus no ischemia (24.4% vs 12.5%). Conversely, off-clamp cases had a higher estimated blood loss (EBL; median: 300 vs 200 ml) but similar complication rates [49]. It is important to note that a proportion of off-clamp cases in these and other reports were performed with simple manual compression of peritumoral parenchyma [48–50]. The application of Kauffman clamps on the kidney was also proposed to achieve hemostasis during tumor resection [51]. The perioperative and functional outcomes of off-clamp PN performed with robotic assistance were retrospectively assessed in a large multi-institutional series of 886 cases. In propensity score-matched analyses, the off-clamp patients had a significantly shorter mean operative time, a higher EBL, and a smaller decrease in eGFR compared with those with intraoperative ischemia (2% vs 6%; p = 0.008) [52]. More recently, Porpiglia et al [53] used renal scans to compare the postoperative RF after LPN with clamping of the renal artery 30 min and is only partially reversible. The functional impairment of the operated kidney is significantly worse with WIT >32 min. Preoperative RF and percent of functional volume preservation are the primary determinants of long-term functional outcomes in patients with normal preoperative RF who have ischemia time within acceptable limits. RF changes did not correlate with ischemia duration. Renal structural changes were much less severe than observed in animal models that used similar duration of ischemia. Acute kidney injury biomarkers were only mildly elevated and did not correlate with RF or ischemia duration. WIT did not have a clinically significant impact on global RF after LPN WIT and endophytic tumor location are associated with a statistically significant loss of differential RF, but only in the group who experienced a WIT >30 min. While total RF is almost unaffected after surgery, a WIT >25 min leads to a significant decrease in effective renal plasma flow on the operated side. WIT as a continuous variable is associated with greater loss of RF. ROC analysis identifies 25 min as a safe WIT cut off. Loss of RF occurs within 3 mo and remains stable until 12 mo after LPN. Intraoperative, visually estimated preserved parenchyma volume, radiologic tumor size, and procedure type significantly correlate with postoperative unilateral RF at univariable analysis. No factor is an independent predictor at multivariable analysis. Renal volume reduction, tumor location, and patient age are independent predictors of postoperative RF at multivariable analysis.
4
Mean: 3.4 1.8
* §
39
OPN/LPN
To assess a novel method to estimate the percent of functional volume preservation and to assess its effect on postoperative functional outcomes
Median CIT: 38.5 Median WIT: 24.5
Median: 3.5
40
OPN
To prospectively assess the renal response to clamp ischemia and reperfusion after PN, including histologic changes on biopsies performed before, during, and after clamping, and changes in biomarkers of acute kidney injury
Mean CIT: 48 Mean WIT: 32.3
Median: 4.1
401
LPN
Median WIT: 29
Median: 2.5
56
LPN
To assess the influence of renal ischemia on long-term global RF assessed with eGFR To evaluate the effect of WIT and other factors on differential RF of the operated kidney assessed by using renal scans (preoperative, 10 d postoperative)
Mean: 30 9
Mean: 3.2 1.6
**
32
OPN (n = 20) LPN (n = 2012)
OPN: 24.2 6.2 LPN: 24.5 7.2
OPN: 2.5 0.6 LPN: 2.9 1.1
* §
53
LPN
To evaluate the differential RF of the operated kidney by using renal scans (preoperative; 1 wk and 6 mo postoperative) To assess the effects of WIT on RF after LPN in patients with a normal contralateral kidney by using renal scans (preoperative; 3 and 6 mo postoperative)
Mean: 21.9
Mean: 3.0
65
OPN (n = 35) LPN (n = 30)
To retrospectively evaluate predictors of postoperative unilateral RF by using renal scans (preoperative, 1 mo postoperative)
OPN: 29.8 9.9 LPN: 28.7 11.2
OPN: 3.8 1.9 LPN: 2.6 1.1
117
OPN (n = 52) LPN (n = 65)
To investigate factors determining RF decrease. (preoperative; 6 mo postoperative)
LPN
To evaluate the long-term effects of WI on RF by using renal scans (preoperative; 3 and 6 mo postoperative; yearly)
OPN: 20.5 (range: 8–35) LPN: 33.5 (range: 13–75) Mean: 27.98 11.12
OPN: 3.72 (range: 0.9–11) LPN: 2.14 (range: 0.8–4) Mean: 3.69 1.39
Porpiglia et al [39]
§
Level of evidence
Mean: 39 8.1
Funahashi et al [40]
Song et al [42]
Main outcomes
To evaluate the impairment of RF of the operated kidney 12 mo after surgery by using renal scans (preoperative; 5 d, 3 mo, and 6 mo postoperative)
*
* §
Tumor size, cm
LPN with WIT >30 min
Shikanov et al [87]
Chan et al [41]
Ischemia time, min
18
Parekh et al [3]
Pouliot et al [38]
Aim of the study
§
Porpiglia et al [37]
Simmons et al [4]
Surgical approach
Porpiglia et al [44]
§
54
Split RF of the operated kidney decreases significantly at 3 mo from surgery and subsequently remains stable during follow-up up to 4 yr. WIT is the only independent predictor of split RF at 4 yr from surgery.
4
2
4 4
4
4
4
EUROPEAN UROLOGY XXX (2015) XXX–XXX
Please cite this article in press as: Volpe A, et al. Renal Ischemia and Function After Partial Nephrectomy: A Collaborative Review of the Literature. Eur Urol (2015), http://dx.doi.org/10.1016/j.eururo.2015.01.025
Table 2 – Recent studies on renal ischemia during partial nephrectomy in the setting of bilateral kidneys
4
4
CIT = cold ischemia time; eGFR = estimated glomerular filtration rate; LPN = laparoscopic partial nephrectomy; OPN = open partial nephrectomy; RF = renal function; WIT = warm ischemia time. Assessment of the amount of preserved/resected renal parenchyma was included in the analysis of predictors of postoperative renal functional outcomes. * Assessment of preoperative renal function was included in the analysis of predictors of postoperative renal functional outcomes. ** Analysis of predictors of postoperative renal functional outcomes not performed. §
7
Study
Patients, no.
Thompson et al [48]
**
Kopp et al [49]
Smith et al [50]
**
Ng et al [55]
**
**
Shao et al [58]
**
Ischemia time, min
OPN (n = 411) To compare the short- and long- Median: 21 (range: 4–55) LPN (n = 47) term renal effects of WI vs no ischemia in patients with a solitary kidney
Clamped PN (n = 164) Clampless PN (n = 64)
OPN
Clamped PN (n = 49) RAPN Clampless PN (n = 283)
Tumor size, cm
Nephrometry score (mean)
Mean: 3.4 Mean: 2.5
–
Mean: 24.5 0
Median: 3.5 Median: 4.0
6.9 1.5 6.4 1.5
Mean: 20 0
Median: 3.0 Median: 2.8
–
To evaluate the functional outcomes of RAPN with and without hilar clamping in a propensity score matched analysis To compare postoperative RF of clampless vs clamped LPN (WIT 30 min in 82.5% of the cases [3]. The authors showed greater-than-expected resistance to ischemia time of human kidneys, with little or no acute RF loss in the early postoperative period. Progressive levels of ischemia up to 61 min had no effect on the injury produced, which was assessed functionally by sCr and cystatin C levels, structurally by light and electron microscopy and immunofluorescence analysis, and by biomarkers excreted in the urine [3]. The strength of this prospective study is that pathologists who evaluated renal structure and biomarkers were blinded to the clinical results and the duration of ischemia. In contrast, the study is limited by the lack of follow-up beyond the hospital duration of a few days, by the presence of a mixed population of patients who underwent cold and warm ischemia, by the lack of information on tumor complexity and estimated volume of preserved parenchyma, and by the absence of RF scans to evaluate contributions from the contralateral kidney. At present, efforts should be always made to minimize ischemia time when planning surgery, especially with imperative indications. Based on level 3–4 evidence from several studies, 20–25 min represents the most accurate cut-off to separate patients who do and do not develop short- and long-term RF decline after PN [15,33,34,39,40, 64,65] (Tables 1 and 2). The temporal trend of loss of RF has been diffusely investigated, especially in the setting of bilateral kidneys. RF appears to decrease immediately after PN and to partially recover to reach a new steady state, generally within 3 wk to 3 mo after PN [39]. It was suggested that the longer the period of RF decline after PN, the worse the nadir and the ultimate GFR. However, RF appears to remain stable after 3 mo from surgery up to 4 yr, according to recent data [43]. The use of cold ischemia is variable and depends on the institution and surgeon. In general, cold ischemia has been used liberally in OPN for those cases where a longer clamping time was expected. Surface hypothermia is generally instituted immediately after vascular clamping and maintained for 10 min before commencing tumor resection [66]. Indeed, there is clear evidence of the protective role of renal cooling with respect to functional injury, with longer periods of cold ischemia harming the nephrons similarly to shorter periods of warm ischemia [5,67]. Yossepowitch et al [68] analyzed RF with eGFR in 592 OPNs with a median CIT of 35 min. At multivariable analysis, CIT was significantly associated with early postsurgical eGFR changes, but not with a significant eGFR decrease 12 mo after surgery [68]. According to Iida et al, a CIT
