- Email: [email protected]
Laparoscopic Partial Nephrectomy in Patients with Compromised Renal Function
Endourology/MIS Laparoscopic Partial Nephrectomy in Patients with Compromised Renal Function Jose R. Colombo, JR., Georges-Pascal Haber, and Inderbir S. Gill OBJECTIVES METHODS
RESULTS
CONCLUSIONS
To present outcomes of laparoscopic partial nephrectomy (LPN) in patients with compromised baseline renal function. Of 485 patients undergoing LPN between September 1999 and August 2005 at our institution, 48 (10%) had compromised baseline renal function, defined as serum creatinine 1.5mg/dL or greater (group I). Outcomes were compared with 437 patients undergoing LPN with normal baseline renal function (serum creatinine less than 1.5 mg/dL, group II). Both groups were compared regarding perioperative data, complications, and renal functional and oncologic outcomes. Group i patients were older (67.6 versus 58.6 years, P ⬍0.001) and had higher American Society of Anesthesiologists scores (2.8 versus 2.4, P ⬍0.001), higher Charlson Comorbidity Index (1.9 versus 0.7, P ⬍0.001), and larger tumors (3.3 versus 2.7 cm, P ⫽ 0.01). Intraoperative data, postoperative outcomes, overall complications, and pathologic data were similar between groups. At a mean follow-up of 21 months, the deterioration in serum creatinine and estimated glomerular filtration rate was similar between groups (P ⫽ 0.99 and 0.89, respectively). Dialysis was required in 5 patients (10%) in group I and 3 patients (0.6%) in group II (P ⬍0.001). Within group I, older patients (older than 70 years) with prolonged warm ischemia (greater than 30 minutes) had significantly worse renal functional outcomes. Comparing groups I and II, estimated 5-year overall survival was 78% versus 90% (log rank ⫽ 0.01) and cancer-specific survival was 100% versus 98% (log rank ⫽ 0.65). Older patients with compromised renal function and warm ischemia time greater than 30 minutes are at high risk for renal dysfunction after LPN. Alternate nephron-sparing methods including hypothermia or probe-ablation should be considered in these patients. UROLOGY 71: 1043–1048, 2008. © 2008 Elsevier Inc.
I
ndependent of each other, the incidence of renal cancer and end-stage renal disease is increasing in the United States.1,2 Approximately 8% of the community population has renal dysfunction, which correlates with advancing age, diabetes, and hypertension.3 Whenever feasible from an anatomic and technical standpoint, elective nephron-sparing surgery is preferred for patients with unilateral small renal mass4 and is imperative in such patients with baseline compromised renal function. Within the past decade, laparoscopic partial nephrectomy (LPN), and energy-based therapies (cryoablation and radiofrequency ablation) have emerged as minimally invasive therapeutic options for patients with a small renal mass. Of these, LPN provides durable 5-year oncologic and renal functional outcomes,5 whereas the other modalities still await reliable long-term data.
From the Section of Laparoscopic and Robotic Surgery, Glickman Urological Institute, Cleveland Clinic, Cleveland, Ohio Reprint requests: Jose R. Colombo, Jr., M.D., Section of Laparoscopic and Robotic Surgery, Glickman Urological Institute, Cleveland Clinic, 9500 Euclid Avenue, A100, Cleveland, OH 44195. E-mail: [email protected] Submitted: November 21, 2006, accepted (with revisions): November 8, 2007
© 2008 Elsevier Inc. All Rights Reserved
The impact of warm ischemia on renal function in patients with preexisting renal insufficiency undergoing LPN has not been previously reported to our knowledge. We evaluated perioperative and functional outcomes of LPN in patients with abnormal baseline renal function (defined as serum creatinine 1.5 mg/dL or greater), and compared these data with a group of patients with normal baseline renal function who underwent LPN for a solitary, small renal mass.
MATERIAL AND METHODS Between September 1999 and August 2005, 485 consecutive patients underwent LPN for a solitary, clinically organ-confined renal tumor at our institution. Of these, 48 patients (10%) had preoperatively abnormal renal function (group I) as defined by serum creatinine level 1.5 mg/dL or greater (normal, 0.7 to 1.4 mg/dL), and 437 patients (90%) had normal baseline renal function (group II). All data were prospectively collected and maintained with institutional review board approval. Indication for LPN was deemed imperative in patients with underlying renal dysfunction, solitary kidney, bilateral tumors, or anatomic compromise; and elective in patients with small renal mass and 0090-4295/08/$34.00 doi:10.1016/j.urology.2007.11.022
1043
Table 1. Baseline demographics and perioperative data of group I (abnormal renal function) and group II (normal renal function)
No. of patients (%) Age (yr) Male (%) Body mass index American Society of Anesthesiology score Charlson comorbidity index Comorbidities Coronary artery disease Hypertension Diabetes COPD Metastatic cancer Ulcerative peptic disease Abnormal hepatic function Right kidney (%) Tumor size (cm) Central tumors (%) Indication for LPN Imperative (%) Elective (%) Solitary kidney (%) Bilateral tumors (%) Transperitoneal approach (%) Intraoperative IV fluids (cc) Intraoperative urine output (mL) Hilar control (%) Estimated blood loss (mL) Warm ischemia time (min) Total operative time (hrs) Specimen weight (g) Hospital stay (days) Oral intake (days) Ambulation (days) Malignancy on pathology (%) Follow-up (mo)
Group I (Mean ⫾ SD)
Group II (Mean ⫾ SD)
P-Value
48 (10) 67.6 ⫾ 11 36 (75) 29.6 ⫾ 5.6 2.8 ⫾ 0.7 1.9 ⫾ 1.7
437 (90) 58.6 ⫾ 12.6 260 (59) 29.3 ⫾ 6.8 2.4 ⫾ 0.7 0.7 ⫾ 1.1
– ⬍0.001 0.12 0.70 ⬍0.001 ⬍0.001
13 (27) 7 (14) 20 (41) 1 (2) 1 (2) 2 (4) 4 (8) 32 (66%) 3.3 ⫾ 1.5 15 (31)
52 (12) 43 (9) 107 (24) 30 (7) 4 (1) 73 (16) 0 (0) 244 (55%) 2.7 ⫾ 1.3 140 (32)
0.003 0.01 0.30 0.19 0.44 0.02 ⬍0.001 0.15 0.01 0.89
48 (100) 0 7 (14) 15 (31) 33 (69) 4185 ⫾ 1412 598 ⫾ 387 48 (100%) 226 ⫾ 249 28.6 ⫾ 11.5 3.5 ⫾ 1.3 63 ⫾ 82 4.3 ⫾ 6 1.6 ⫾ 1.3 1.5 ⫾ 1.1 40 (84) 24 ⫾ 19
89 (20) 348 (80) 16 (4) 73 (16) 296 (67) 4560 ⫾ 1527 878 ⫾ 619 432 (99%) 258 ⫾ 435 31.3 ⫾ 11 3.4 ⫾ 1 51 ⫾ 60 3.1 ⫾ 2.9 1.3 ⫾ 1.0 1.5 ⫾ 0.7 312 (71) 21 ⫾ 19
⬍0.001 ⬍0.001 0.03 0.02 0.79 0.10 0.003 0.92 0.62 0.14 0.67 0.68 0.24 0.19 0.84 0.07 –
COPD, chronic obstructive pulmonary disease; IV, intravenous; LPN, laparoscopic partial nephrectomy; SD, standard deviation.
normal-appearing contralateral kidney. Table 1 presents comparative preoperative demographics. Our technique of LPN, detailed elsewhere previously,6,7 incorporated transient en-bloc renal hilar control, real-time contact ultrasonography, cold tumor excision with endoshears, reconstruction of the pelvicaliceal system, and sutured hemostatic renal parenchymal re-approximation over a Surgicel bolster with adjunctive use of biologic hemostatic agent (Floseal). Complications were categorized as intraoperative or postoperative. Intraoperative complications were grouped in two categories: hemorrhage (defined as blood loss higher than 1 L or any blood transfusion) and visceral injury (defined as injury to surrounding organs or structures). Postoperative complications were divided into nine categories: ileus (no oral intake, any use of nasogastric tube, nausea or vomiting beyond 48 hours postoperatively), thromboembolic (deep vein thrombosis and pulmonary embolism), pulmonary (symptomatic atelectasia, pneumonia, or pneumothorax), cardiovascular (new onset atrial fibrillation, or myocardial infarction), renal (necessity of dialysis), procedure-related (urinary extravasation, hemorrhage, secondary surgical procedures), infectious (port site infection), incisional hernia, and miscellaneous (including metabolic and neurological issues). 1044
We obtained follow-up data from patient charts, radiographic reports, direct phone calls to patients or patient families, and the Social Security Death Index. The mean follow-up was 24 ⫾ 19 months for group I and 21 ⫾ 19 months for group II. We compared both groups on categorical variables using Chisquare test or Fisher’s exact test, and on normally distributed continuous variables using Student t-test or Wilcoxon rank sum test for the non-normally distributed continuous variables.
RESULTS Group I had older patients (P ⬍0.001), higher American Society of Anesthesiology (ASA) class (P ⬍0.001), and higher Charlson Comorbidity Index (P ⬍0.001) compared with group II (Table 1). Group I patients also had larger tumor size (3.3 cm versus 2.7 cm, P ⫽ 0.01), greater incidence of solitary kidneys (14% versus 4%; P ⫽ 0.03), and bilateral tumors (31% versus 16%; P ⫽ 0.02). Intraoperative outcomes were similar between groups regarding the laparoscopic approach employed, performance of hilar clamping, blood loss, warm ischemia time, UROLOGY 71 (6), 2008
Table 2. Complications and pathologic results of group I (abnormal renal function) and group II (normal renal function)
Intraoperative (%) Hemorrhage Visceral injury Postoperative (%) Ileus Thromboembolic Hemorrhage Urine leakage Other Pulmonary Cardiovascular Dialysis Infectious Incisional hernia Miscellaneous Blood transfusion (%) Open conversion (%) Pathology (%) RCC Liposarcoma Benign RCC histology (%) Clear cell Papillary Chromophobe Sarcomatoid Unclassified Fuhrman grade (%) I II III IV n/a Pathologic stage (%) T1a T1b T2 T3a Positive margins for RCC (%)
Group I
Group II
P-Value
3 (6) 2 (4) 1(2) 11 (23) 1 (2) 1 (2) 2 (4) 1 (2) 0 1 (2) 0 5 (10) 0 0 0 4 (8) 1 (2)
32 (7) 21 (5) 11 (2) 85 (19) 20 (4) 5 (1) 15 (3) 8 (2) 3 (0.6) 14 (3) 7 (1) 3 (0.6) 3 (0.5) 3 (0.5) 4 (1) 13 (2) 6 (2)
0.78 0.93 0.85 0.80 0.37 0.60 0.94 0.91 0.41 0.65 0.22 ⬍0.001 0.42 0.42 0.36 0.09 0.79 ⬍0.001
39 (81) 1 (3) 8 (16)
312 (65) – 125 (35)
17 (45) 19 (49) 1 (2) 1 (2) 1 (2)
203 (65) 76 (24) 30 (10) – 3 (1)
1 (2) 24 (65) 11 (29) 0 2 (4)
31(10) 176 (57) 79 (25) 13 (4) 13 (4)
29 (73) 8 (20) 1 (2) 2 (5) 0
274 (88) 23 (7) 1 (0.5) 14 (4.5) 3 (0.6)
⬍0.001
0.31
0.38
0.39
RCC, renal cell carcinoma.
and total operative time (Table 1). Although the volume of intravenous fluids administered was comparable, intraoperative urine output was significantly lower in group I. Postoperatively, resumption of diet and ambulation, and hospital stay were comparable. Tumors in group I were more commonly renal cell carcinoma on pathology (Table 2). Overall perioperative complications were comparable between groups (Table 2). By definition, group I had a higher preoperative mean serum creatinine level than group II (1.9 versus 0.9 mg/dL; P ⬍0.001) and consequently a higher postoperative serum creatinine level (2.2 versus 1.1 mg/dL; P ⬍0.001). Nevertheless, the percent increase in postoperative serum creatinine was similar: 20% versus 21% (P ⫽ 0.99). Similarly, group I had lower glomerular filtration rate preoperatively (37.7 versus 85.1 mL/min; P ⬍0.001) and therefore postoperatively (31 versus 70.3 mL/min; P ⬍0.001); however, the percent postoperative deUROLOGY 71 (6), 2008
crease was comparable (16% versus 16%; )P ⫽ 0.99). This fact mirrored the similar amount of renal parenchyma excised: specimen weight was 63 ⫾ 82 g in group I and 51 ⫾ 60 g in group II (P ⫽ 0.68). Univariate analysis showed age, ASA score, bilateral tumors, Charlson Comorbidity Index, tumor size, and baseline serum creatinine of 1.5 mg/dL or greater to be associated with postoperative renal insufficiency (serum creatinine greater than 2 mg/dL). Dialysis was required postoperatively in 5 patients (10%) in group I (temporary 6%, permanent 4%) and in 3 patients (0.6%) in group II (temporary 0.4%, permanent 0.2%). This difference was statistically significant (P ⬍0.001). The patient in group II who required dialysis had a large tumor in a solitary kidney, and the 2 patients with temporary dialysis had significant morbidities (age greater than 70 years, ASA score of 3, and Charlson Comorbidity Index of 5). Solitary kidney (P ⫽ 0.04), baseline serum creatinine (P ⬍0.001), and baseline glomerular filtration rate (GFR) (P ⫽ 0.007) were significantly associated with postoperative dialysis. Of these, only solitary kidney (adjusted odds ratio, 6.1; 95% confidence interval, 1 to 31; P ⫽ 0.03) was identified as an independent risk factor for dialysis on logistic regression. Group I had worse estimated 5-year overall survival (78% versus 90%; P ⫽ 0.01) but similar estimated 5-year cancer-specific survival (100% versus 98%; P ⫽ 0.65). Solitary kidney was present in 7 patients (14%) in group I and 16 patients (3%) in group II (P ⫽ 0.003) (Table 3). Baseline, intraoperative, and postoperative data were comparable between these two subgroups. Although by definition, preoperative—and consequently, postoperative—renal function was inferior in group I, the percent deterioration postoperatively was comparable between subgroups. Dialysis was necessary in only 1 patient in each subgroup (P ⫽ 0.52). Within group I, comparing outcomes of patients with mild renal dysfunction (defined as serum creatinine 1.5 to 1.9 mg/dL) and moderate renal dysfunction (defined as serum creatinine of 2 mg/dL or greater), tumor size was larger in the latter subgroup (2.9 cm versus 4.1 cm; P ⫽ 0.009). Despite the significantly worse baseline renal function in group I, the postoperative functional deterioration was equivalent between subgroups. We also evaluated the impact of warm ischemia time (30 minutes or less versus greater than 30 minutes) within group I patients. Although, percent increase in serum creatinine tended to be higher in patients undergoing warm ischemia greater than 30 minutes, the difference was not statistically significant (12.6% versus 22.4%; P ⫽ 0.14). Finally, within group I, patients older than 70 years with warm ischemia time greater than 30 minutes had significantly greater deterioration in serum creatinine (P ⫽ 0.02) and GFR (P ⫽ 0.03) compared with younger patients with shorter warm ischemia time (Table 4). 1045
Table 3. Patients with solitary kidney (n ⫽ 23): baseline demographics and outcomes between group I (abnormal renal function) and group II (normal renal function)
No. Age (yr) BMI ASA* CCI* Tumor size (cm) Estimated blood loss (mL) Warm ischemia (min) Operative time (hr) Specimen weight (g) Hospital stay (days) Oral intake (days) Ambulation (days) Intraoperative complications (%) Postoperative complications (%) Dialysis (%) Overall survival (%) Follow-up (mo) Serum creatinine (mg/dL) Preoperative Postoperative % Increase GFR (mL/min) Preoperative Postoperative % Decrease
Group I (Mean ⫾ SD)
Group II (Mean ⫾ SD)
P-Value
7 (14%) 71.2 ⫾ 13.9 33.8 ⫾ 9.6 3 (3) 1 (1–5) 4.2 ⫾ 2 200 ⫾ 189 29.8 ⫾ 10.3 3.5 ⫾ 1 83 ⫾ 94 4.7 ⫾ 1.3 1.2 ⫾ 1.0 2⫾1 0 2 (28) 1 (14) 83 25 ⫾ 17
16 (3%) 58.7 ⫾ 12 31.8 ⫾ 5.1 3 (2–3) 0 (0–2) 3.1 ⫾ 1.1 345 ⫾ 416 29.2 ⫾ 13.7 3.9 ⫾ 1.5 31 ⫾ 23 3.6 ⫾ 2.7 2.1 ⫾ 1.9 2.3 ⫾ 1.3 1 (6) 5 (25) 1 (6) 83 27 ⫾ 20
0.003 0.04 0.58 0.16 0.05 0.13 0.44 0.91 0.65 0.11 0.38 0.42 0.78 0.38 0.80 0.52 0.99† –
1.7 ⫾ 0.2 1.8 ⫾ 0.2 12.8
0.9 ⫾ 0.1 1.4 ⫾ 0.6 50.8
⬍0.001 0.1 0.11
41.2 ⫾ 7.6 36.2 ⫾ 10.2 12
92.8 ⫾ 19.2 70.1 ⫾ 16.7 23
⬍0.001 ⬍0.001 0.20
ASA, American Society of Anesthesiology; BMI, body mass index; CCI, Charlson Comorbidity Index; GFR, glomerular filtration rate. * Median (range). † Log rank.
COMMENT In the management of patients with a small renal tumor and chronic renal insufficiency, preservation of nephron mass is imperative. During partial nephrectomy, warm ischemia may be more deleterious to the function of a baseline compromised kidney vis-à-vis a normal kidney. To our knowledge, no prior report, open or laparoscopic, has specifically focused on outcomes of partial nephrectomy with hilar clamping in patients with preexisting renal dysfunction. Salient findings of our study are as follows. Patients with preoperative renal insufficiency were older, less healthy, and deemed to have higher anesthetic risk (P ⬍0.001). This group also had larger tumor size and a higher percentage of solitary kidneys and bilateral tumors. Despite the above, intraoperative parameters, postoperative outcomes, overall complications, and histopathologic data were comparable between groups. Of note, duration of hilar clamping (warm ischemia time) and amount of kidney parenchyma excised (specimen weight) were also similar between groups. Although the preoperative, and consequently the postoperative, renal function was expectedly inferior in group I patients, the percent postoperative reduction in renal function appeared to be similar between groups. Within group I, subgroup outcomes analysis of patients with baseline serum creatinine 1.5 to 1.9 mg/dL versus those with serum creatinine 2 mg/dL or greater also revealed comparable deterioration in renal function. Fi1046
nally, among patients with baseline renal dysfunction, those aged greater than 70 years and undergoing warm ischemia more than 30 minutes had the greatest postoperative deterioration of renal function (Table 4). These data indicate that older patients (greater than 70 years) with longer warm ischemia time (more than 30 minutes) are at risk for postoperative renal function deterioration after LPN with hilar clamping. This high-risk subgroup of patients should preferably be treated with alternate nephron-sparing strategies with use of hypothermia, or probe ablative therapies such as cryoablation or radiofrequency ablation. Renal functional outcomes after partial nephrectomy are documented in the literature. In patients with a normal contralateral kidney, open partial nephrectomy resulted in a lower incidence of chronic renal insufficiency (defined as serum creatinine greater than 2 mg/dL) compared with radical nephrectomy (11.6% versus 22.4%; relative risk, 3.7).8 Similarly, in patients with a small (4 cm or less) renal tumor and normal contralateral kidney, postoperative serum creatinine was lower after open partial versus radical nephrectomy (1.0 versus 1.5 mg/dL; P ⬍0.001).9 Thompson et al. documented chronic renal insufficiency/renal failure in 14.6% of historic and 8.1% of contemporary patients after open partial nephrectomy.10 In Desai’s functional analysis of our 179 patients, although no clinically apparent sequelae were noted with a warm ischemia time of up to 30 minutes, advancing age (greater than 70 years) and preexisting azotemia inUROLOGY 71 (6), 2008
Table 4. Renal functional outcomes between group I (abnormal renal function) and group II (normal renal function) and impact of warm ischemia time and patient age on ultimate renal function Group I Serum creatinine (mg/dL) Preoperative Postoperative % Change Estimated GFR* (mL/min) Preoperative Postoperative % Change Dialysis Temporary Permanent
Serum creatinine Preoperative Postoperative % Increase GFR Preoperative Postoperative % Decrease
Group II
P-Value
1.9 ⫾ 0.4 2.2 ⫾ 0.8 20% (95% CI, 12.7 to 29.2)
0.9 ⫾ 0.2 1.1 ⫾ 0.6 21% (95% CI, 17.9 to 24)
⬍0.001 ⬍0.001 0.99
37.7 ⫾ 9.1 31 ⫾ 9.7 16% (95% CI, ⫺22 to ⫺11) 5 (10%) 3 (6%) 2 (4%)
85.1 ⫾ 18.9 70.3 ⫾ 19.8 16% (95% CI, ⫺18.2 to ⫺13.9) 3 (0.6%) 2 (0.4%) 1 (0.2%)
⬍0.001 ⬍0.001 0.89 ⬍0.001 ⬍0.001 ⬍0.001
Warm Ischemia Time ⬍30 min Subgroup Ia Subgroup Ib (Age ⬍70 yr) (Age ⬎70 yr) P-Value
Warm Ischemia Time ⬎30 min Subgroup Ic Subgroup Id (Age ⬍70 yr) (Age ⬎70 yr) P-Value
2.0 ⫾ 0.5 2.1 ⫾ 0.4 10.2 ⫾ 11.9†
1.7 ⫾ 0.3 2.2 ⫾ 0.7 17.7 ⫾ 26.6
0.12 0.83 0.34
1.8 ⫾ 0.3 2.1 ⫾ 0.9 16.8 ⫾ 24.3
32 ⫾ 10 30 ⫾ 8 11.7 ⫾ 16.4‡
38 ⫾ 7 32 ⫾ 12 14 ⫾ 28.6
0.16 0.63 0.73
40 ⫾ 7 36 ⫾ 8 9.3 ⫾ 23
1.7 ⫾ 0.4 2.2 ⫾ 0.6 25.4 ⫾ 18†
0.66 0.68 0.54
40 ⫾ 7 29 ⫾ 7 25.6 ⫾ 12.8‡
0.88 0.13 0.13
Abbreviations as in previous tables. * Glomerular filtration rate ⫽ [[140 ⫺ age (yr)] ⫻ weight (kg)]/[72 ⫻ serum Cr (mg/dL)] (multiply by 0.85 for women). Group I (n ⫽ 48): Patients with baseline serum creatinine greater than 1.5 mg/dL. Subgroup Ia (n ⫽ 13): Within group I, patients aged less than 70 years with warm ischemia time less than 30 minutes. Subgroup Ib (n ⫽ 12): Within group I, patients aged greater than 70 years with warm ischemia time less than 30 minutes. Subgroup Ic (n ⫽ 12): Within group I, patients aged less than 70 years with warm ischemia time greater than 30 minutes. Subgroup Id (n ⫽ 11): Within group I, patients aged greater than 70 years with warm ischemia time greater than 30 minutes. † P-Value (subgroup Ia versus Id) ⫽ 0.02. ‡ P-Value (subgroup Ia versus Id) ⫽ 0.03.
creased the risk of postoperative renal dysfunction, particularly when the warm ischemia time exceeded 30 minutes.11 In the study recently published by Kobayashi et al., the authors confirmed this result using scintigraphic renal analysis.12 In 22 patients with a solitary kidney, the reduction of renal function (approximately 30% increase in serum creatinine) appeared commensurate with the amount of renal parenchyma excised (approximately 23%).13 In the current study, overall survival was inferior in group I, which is not surprising given the higher prevalence of preexisting comorbidities. However, estimated 5-year cancer-specific survival was similar between groups (100% versus 98%; P ⫽ 0.65). We recognize the limitations of our study. Although collected prospectively, the data were analyzed retrospectively. Serum creatinine is a less than ideal parameter to investigate renal function. Renal scan data were not available uniformly, precluding postoperative determination of differential function of the operated kidney. Similarly, data regarding 24-hour urinary protein excretion are lacking, which would add to our understanding of the impact of warm ischemia on the compromised kidney. The strength of this report is the large number of patients with abnormal renal function undergoing LPN with relatively long functional follow-up. UROLOGY 71 (6), 2008
Certain considerations are pertinent when performing LPN in patients with renal dysfunction. Investigation and optimization of preoperative cardiopulmonary status are essential. Renal perfusion and diuresis are maximized by judicious administration of intravenous fluids and diuretics. In our study, despite comparable intravenous fluid administration, intraoperative urine output was significantly lesser in the patients with renal dysfunction. We typically administer 12.5 g of mannitol at the time of hilar dissection and a repeat 12.5 g mannitol plus 20 mg of furosemide 2 to 3 minutes before hilar unclamping. Hilar control is efficiently achieved by en bloc clamping. Every effort is made to minimize renal ischemia time. Preplanning of maneuvers for tumor excision and renal repair, an experienced team, and complete comfort in the laparoscopic environment are essential in this regard.
CONCLUSION Older patients with compromised renal function and warm ischemia time greater than 30 minutes are at high risk for renal dysfunction after LPN with hilar clamping. Alternate nephron-sparing methods including hypothermia or nonclamping probe-ablation should be considered in this patient subset. 1047
References 1. Chow WH, Devesa SS, Warren JL, et al: Rising incidence of renal cell cancer in the United States. JAMA 281: 1628-1631, 1999. 2. Culleton BF, Larson MG, Evans JC, et al: Prevalence and correlates of elevated serum creatinine levels: the Framingham Heart Study. Arch Intern Med 159: 1785-1790, 1999. 3. Iseki K, Ikemiya Y, and Fukiyama K: Risk factors of end-stage renal disease and serum creatinine in a community-based mass screening. Kidney Int 51: 850-854, 1997. 4. Becker F, Siemer S, Humke U, et al: Elective nephron sparing surgery should become standard treatment for small unilateral renal cell carcinoma: long-term survival data of 216 patients. Eur Urol 49: 308-313, 2006. 5. Lane BR, and Gill IS: Five-year outcomes of laparoscopic partial nephrectomy. J Urol 177: 70-74, 2007. 6. Gill IS, Desai MM, Kaouk JH, et al: Laparoscopic partial nephrectomy for renal tumor: duplicating open surgical techniques. J Urol 167: 469-474, 2002. 7. Haber GP, and Gill IS: Laparoscopic partial nephrectomy: contemporary technique and outcomes. Eur Urol 49: 660-665, 2006.
1048
8. Lau WK, Blute ML, Weaver AL, et al: Matched comparison of radical nephrectomy vs. nephron-sparing surgery in patients with unilateral renal cell carcinoma and a normal contralateral kidney. Mayo Clin Proc 75: 1236-1242, 2000. 9. McKiernan J, Simmons R, Katz J, et al: Natural history of chronic renal insufficiency after partial and radical nephrectomy. Urology 59: 816-820, 2002. 10. Thompson RH, Leibovich BC, Lohse CM, et al: Complications of contemporary open nephron sparing surgery: a single institution experience. J Urol 174: 855-858, 2005. 11. Desai MM, Gill IS, Ramani AP, et al: The impact of warm ischaemia on renal function after laparoscopic partial nephrectomy. BJU Int 95: 377-383, 2005. 12. Kobayashi Y, Usui Y, Shima M, et al: Evaluation of renal function after laparoscopic partial nephrectomy with renal scintigraphy using 99mtechnetium-mercaptoacetyltriglycine. Int J Urol 13: 13711374, 2006. 13. Gill IS, Colombo JR Jr, Moinzadeh A, et al: Laparoscopic partial nephrectomy in solitary kidney. J Urol 175: 454-458, 2006.
UROLOGY 71 (6), 2008
RESULTS
CONCLUSIONS
To present outcomes of laparoscopic partial nephrectomy (LPN) in patients with compromised baseline renal function. Of 485 patients undergoing LPN between September 1999 and August 2005 at our institution, 48 (10%) had compromised baseline renal function, defined as serum creatinine 1.5mg/dL or greater (group I). Outcomes were compared with 437 patients undergoing LPN with normal baseline renal function (serum creatinine less than 1.5 mg/dL, group II). Both groups were compared regarding perioperative data, complications, and renal functional and oncologic outcomes. Group i patients were older (67.6 versus 58.6 years, P ⬍0.001) and had higher American Society of Anesthesiologists scores (2.8 versus 2.4, P ⬍0.001), higher Charlson Comorbidity Index (1.9 versus 0.7, P ⬍0.001), and larger tumors (3.3 versus 2.7 cm, P ⫽ 0.01). Intraoperative data, postoperative outcomes, overall complications, and pathologic data were similar between groups. At a mean follow-up of 21 months, the deterioration in serum creatinine and estimated glomerular filtration rate was similar between groups (P ⫽ 0.99 and 0.89, respectively). Dialysis was required in 5 patients (10%) in group I and 3 patients (0.6%) in group II (P ⬍0.001). Within group I, older patients (older than 70 years) with prolonged warm ischemia (greater than 30 minutes) had significantly worse renal functional outcomes. Comparing groups I and II, estimated 5-year overall survival was 78% versus 90% (log rank ⫽ 0.01) and cancer-specific survival was 100% versus 98% (log rank ⫽ 0.65). Older patients with compromised renal function and warm ischemia time greater than 30 minutes are at high risk for renal dysfunction after LPN. Alternate nephron-sparing methods including hypothermia or probe-ablation should be considered in these patients. UROLOGY 71: 1043–1048, 2008. © 2008 Elsevier Inc.
I
ndependent of each other, the incidence of renal cancer and end-stage renal disease is increasing in the United States.1,2 Approximately 8% of the community population has renal dysfunction, which correlates with advancing age, diabetes, and hypertension.3 Whenever feasible from an anatomic and technical standpoint, elective nephron-sparing surgery is preferred for patients with unilateral small renal mass4 and is imperative in such patients with baseline compromised renal function. Within the past decade, laparoscopic partial nephrectomy (LPN), and energy-based therapies (cryoablation and radiofrequency ablation) have emerged as minimally invasive therapeutic options for patients with a small renal mass. Of these, LPN provides durable 5-year oncologic and renal functional outcomes,5 whereas the other modalities still await reliable long-term data.
From the Section of Laparoscopic and Robotic Surgery, Glickman Urological Institute, Cleveland Clinic, Cleveland, Ohio Reprint requests: Jose R. Colombo, Jr., M.D., Section of Laparoscopic and Robotic Surgery, Glickman Urological Institute, Cleveland Clinic, 9500 Euclid Avenue, A100, Cleveland, OH 44195. E-mail: [email protected] Submitted: November 21, 2006, accepted (with revisions): November 8, 2007
© 2008 Elsevier Inc. All Rights Reserved
The impact of warm ischemia on renal function in patients with preexisting renal insufficiency undergoing LPN has not been previously reported to our knowledge. We evaluated perioperative and functional outcomes of LPN in patients with abnormal baseline renal function (defined as serum creatinine 1.5 mg/dL or greater), and compared these data with a group of patients with normal baseline renal function who underwent LPN for a solitary, small renal mass.
MATERIAL AND METHODS Between September 1999 and August 2005, 485 consecutive patients underwent LPN for a solitary, clinically organ-confined renal tumor at our institution. Of these, 48 patients (10%) had preoperatively abnormal renal function (group I) as defined by serum creatinine level 1.5 mg/dL or greater (normal, 0.7 to 1.4 mg/dL), and 437 patients (90%) had normal baseline renal function (group II). All data were prospectively collected and maintained with institutional review board approval. Indication for LPN was deemed imperative in patients with underlying renal dysfunction, solitary kidney, bilateral tumors, or anatomic compromise; and elective in patients with small renal mass and 0090-4295/08/$34.00 doi:10.1016/j.urology.2007.11.022
1043
Table 1. Baseline demographics and perioperative data of group I (abnormal renal function) and group II (normal renal function)
No. of patients (%) Age (yr) Male (%) Body mass index American Society of Anesthesiology score Charlson comorbidity index Comorbidities Coronary artery disease Hypertension Diabetes COPD Metastatic cancer Ulcerative peptic disease Abnormal hepatic function Right kidney (%) Tumor size (cm) Central tumors (%) Indication for LPN Imperative (%) Elective (%) Solitary kidney (%) Bilateral tumors (%) Transperitoneal approach (%) Intraoperative IV fluids (cc) Intraoperative urine output (mL) Hilar control (%) Estimated blood loss (mL) Warm ischemia time (min) Total operative time (hrs) Specimen weight (g) Hospital stay (days) Oral intake (days) Ambulation (days) Malignancy on pathology (%) Follow-up (mo)
Group I (Mean ⫾ SD)
Group II (Mean ⫾ SD)
P-Value
48 (10) 67.6 ⫾ 11 36 (75) 29.6 ⫾ 5.6 2.8 ⫾ 0.7 1.9 ⫾ 1.7
437 (90) 58.6 ⫾ 12.6 260 (59) 29.3 ⫾ 6.8 2.4 ⫾ 0.7 0.7 ⫾ 1.1
– ⬍0.001 0.12 0.70 ⬍0.001 ⬍0.001
13 (27) 7 (14) 20 (41) 1 (2) 1 (2) 2 (4) 4 (8) 32 (66%) 3.3 ⫾ 1.5 15 (31)
52 (12) 43 (9) 107 (24) 30 (7) 4 (1) 73 (16) 0 (0) 244 (55%) 2.7 ⫾ 1.3 140 (32)
0.003 0.01 0.30 0.19 0.44 0.02 ⬍0.001 0.15 0.01 0.89
48 (100) 0 7 (14) 15 (31) 33 (69) 4185 ⫾ 1412 598 ⫾ 387 48 (100%) 226 ⫾ 249 28.6 ⫾ 11.5 3.5 ⫾ 1.3 63 ⫾ 82 4.3 ⫾ 6 1.6 ⫾ 1.3 1.5 ⫾ 1.1 40 (84) 24 ⫾ 19
89 (20) 348 (80) 16 (4) 73 (16) 296 (67) 4560 ⫾ 1527 878 ⫾ 619 432 (99%) 258 ⫾ 435 31.3 ⫾ 11 3.4 ⫾ 1 51 ⫾ 60 3.1 ⫾ 2.9 1.3 ⫾ 1.0 1.5 ⫾ 0.7 312 (71) 21 ⫾ 19
⬍0.001 ⬍0.001 0.03 0.02 0.79 0.10 0.003 0.92 0.62 0.14 0.67 0.68 0.24 0.19 0.84 0.07 –
COPD, chronic obstructive pulmonary disease; IV, intravenous; LPN, laparoscopic partial nephrectomy; SD, standard deviation.
normal-appearing contralateral kidney. Table 1 presents comparative preoperative demographics. Our technique of LPN, detailed elsewhere previously,6,7 incorporated transient en-bloc renal hilar control, real-time contact ultrasonography, cold tumor excision with endoshears, reconstruction of the pelvicaliceal system, and sutured hemostatic renal parenchymal re-approximation over a Surgicel bolster with adjunctive use of biologic hemostatic agent (Floseal). Complications were categorized as intraoperative or postoperative. Intraoperative complications were grouped in two categories: hemorrhage (defined as blood loss higher than 1 L or any blood transfusion) and visceral injury (defined as injury to surrounding organs or structures). Postoperative complications were divided into nine categories: ileus (no oral intake, any use of nasogastric tube, nausea or vomiting beyond 48 hours postoperatively), thromboembolic (deep vein thrombosis and pulmonary embolism), pulmonary (symptomatic atelectasia, pneumonia, or pneumothorax), cardiovascular (new onset atrial fibrillation, or myocardial infarction), renal (necessity of dialysis), procedure-related (urinary extravasation, hemorrhage, secondary surgical procedures), infectious (port site infection), incisional hernia, and miscellaneous (including metabolic and neurological issues). 1044
We obtained follow-up data from patient charts, radiographic reports, direct phone calls to patients or patient families, and the Social Security Death Index. The mean follow-up was 24 ⫾ 19 months for group I and 21 ⫾ 19 months for group II. We compared both groups on categorical variables using Chisquare test or Fisher’s exact test, and on normally distributed continuous variables using Student t-test or Wilcoxon rank sum test for the non-normally distributed continuous variables.
RESULTS Group I had older patients (P ⬍0.001), higher American Society of Anesthesiology (ASA) class (P ⬍0.001), and higher Charlson Comorbidity Index (P ⬍0.001) compared with group II (Table 1). Group I patients also had larger tumor size (3.3 cm versus 2.7 cm, P ⫽ 0.01), greater incidence of solitary kidneys (14% versus 4%; P ⫽ 0.03), and bilateral tumors (31% versus 16%; P ⫽ 0.02). Intraoperative outcomes were similar between groups regarding the laparoscopic approach employed, performance of hilar clamping, blood loss, warm ischemia time, UROLOGY 71 (6), 2008
Table 2. Complications and pathologic results of group I (abnormal renal function) and group II (normal renal function)
Intraoperative (%) Hemorrhage Visceral injury Postoperative (%) Ileus Thromboembolic Hemorrhage Urine leakage Other Pulmonary Cardiovascular Dialysis Infectious Incisional hernia Miscellaneous Blood transfusion (%) Open conversion (%) Pathology (%) RCC Liposarcoma Benign RCC histology (%) Clear cell Papillary Chromophobe Sarcomatoid Unclassified Fuhrman grade (%) I II III IV n/a Pathologic stage (%) T1a T1b T2 T3a Positive margins for RCC (%)
Group I
Group II
P-Value
3 (6) 2 (4) 1(2) 11 (23) 1 (2) 1 (2) 2 (4) 1 (2) 0 1 (2) 0 5 (10) 0 0 0 4 (8) 1 (2)
32 (7) 21 (5) 11 (2) 85 (19) 20 (4) 5 (1) 15 (3) 8 (2) 3 (0.6) 14 (3) 7 (1) 3 (0.6) 3 (0.5) 3 (0.5) 4 (1) 13 (2) 6 (2)
0.78 0.93 0.85 0.80 0.37 0.60 0.94 0.91 0.41 0.65 0.22 ⬍0.001 0.42 0.42 0.36 0.09 0.79 ⬍0.001
39 (81) 1 (3) 8 (16)
312 (65) – 125 (35)
17 (45) 19 (49) 1 (2) 1 (2) 1 (2)
203 (65) 76 (24) 30 (10) – 3 (1)
1 (2) 24 (65) 11 (29) 0 2 (4)
31(10) 176 (57) 79 (25) 13 (4) 13 (4)
29 (73) 8 (20) 1 (2) 2 (5) 0
274 (88) 23 (7) 1 (0.5) 14 (4.5) 3 (0.6)
⬍0.001
0.31
0.38
0.39
RCC, renal cell carcinoma.
and total operative time (Table 1). Although the volume of intravenous fluids administered was comparable, intraoperative urine output was significantly lower in group I. Postoperatively, resumption of diet and ambulation, and hospital stay were comparable. Tumors in group I were more commonly renal cell carcinoma on pathology (Table 2). Overall perioperative complications were comparable between groups (Table 2). By definition, group I had a higher preoperative mean serum creatinine level than group II (1.9 versus 0.9 mg/dL; P ⬍0.001) and consequently a higher postoperative serum creatinine level (2.2 versus 1.1 mg/dL; P ⬍0.001). Nevertheless, the percent increase in postoperative serum creatinine was similar: 20% versus 21% (P ⫽ 0.99). Similarly, group I had lower glomerular filtration rate preoperatively (37.7 versus 85.1 mL/min; P ⬍0.001) and therefore postoperatively (31 versus 70.3 mL/min; P ⬍0.001); however, the percent postoperative deUROLOGY 71 (6), 2008
crease was comparable (16% versus 16%; )P ⫽ 0.99). This fact mirrored the similar amount of renal parenchyma excised: specimen weight was 63 ⫾ 82 g in group I and 51 ⫾ 60 g in group II (P ⫽ 0.68). Univariate analysis showed age, ASA score, bilateral tumors, Charlson Comorbidity Index, tumor size, and baseline serum creatinine of 1.5 mg/dL or greater to be associated with postoperative renal insufficiency (serum creatinine greater than 2 mg/dL). Dialysis was required postoperatively in 5 patients (10%) in group I (temporary 6%, permanent 4%) and in 3 patients (0.6%) in group II (temporary 0.4%, permanent 0.2%). This difference was statistically significant (P ⬍0.001). The patient in group II who required dialysis had a large tumor in a solitary kidney, and the 2 patients with temporary dialysis had significant morbidities (age greater than 70 years, ASA score of 3, and Charlson Comorbidity Index of 5). Solitary kidney (P ⫽ 0.04), baseline serum creatinine (P ⬍0.001), and baseline glomerular filtration rate (GFR) (P ⫽ 0.007) were significantly associated with postoperative dialysis. Of these, only solitary kidney (adjusted odds ratio, 6.1; 95% confidence interval, 1 to 31; P ⫽ 0.03) was identified as an independent risk factor for dialysis on logistic regression. Group I had worse estimated 5-year overall survival (78% versus 90%; P ⫽ 0.01) but similar estimated 5-year cancer-specific survival (100% versus 98%; P ⫽ 0.65). Solitary kidney was present in 7 patients (14%) in group I and 16 patients (3%) in group II (P ⫽ 0.003) (Table 3). Baseline, intraoperative, and postoperative data were comparable between these two subgroups. Although by definition, preoperative—and consequently, postoperative—renal function was inferior in group I, the percent deterioration postoperatively was comparable between subgroups. Dialysis was necessary in only 1 patient in each subgroup (P ⫽ 0.52). Within group I, comparing outcomes of patients with mild renal dysfunction (defined as serum creatinine 1.5 to 1.9 mg/dL) and moderate renal dysfunction (defined as serum creatinine of 2 mg/dL or greater), tumor size was larger in the latter subgroup (2.9 cm versus 4.1 cm; P ⫽ 0.009). Despite the significantly worse baseline renal function in group I, the postoperative functional deterioration was equivalent between subgroups. We also evaluated the impact of warm ischemia time (30 minutes or less versus greater than 30 minutes) within group I patients. Although, percent increase in serum creatinine tended to be higher in patients undergoing warm ischemia greater than 30 minutes, the difference was not statistically significant (12.6% versus 22.4%; P ⫽ 0.14). Finally, within group I, patients older than 70 years with warm ischemia time greater than 30 minutes had significantly greater deterioration in serum creatinine (P ⫽ 0.02) and GFR (P ⫽ 0.03) compared with younger patients with shorter warm ischemia time (Table 4). 1045
Table 3. Patients with solitary kidney (n ⫽ 23): baseline demographics and outcomes between group I (abnormal renal function) and group II (normal renal function)
No. Age (yr) BMI ASA* CCI* Tumor size (cm) Estimated blood loss (mL) Warm ischemia (min) Operative time (hr) Specimen weight (g) Hospital stay (days) Oral intake (days) Ambulation (days) Intraoperative complications (%) Postoperative complications (%) Dialysis (%) Overall survival (%) Follow-up (mo) Serum creatinine (mg/dL) Preoperative Postoperative % Increase GFR (mL/min) Preoperative Postoperative % Decrease
Group I (Mean ⫾ SD)
Group II (Mean ⫾ SD)
P-Value
7 (14%) 71.2 ⫾ 13.9 33.8 ⫾ 9.6 3 (3) 1 (1–5) 4.2 ⫾ 2 200 ⫾ 189 29.8 ⫾ 10.3 3.5 ⫾ 1 83 ⫾ 94 4.7 ⫾ 1.3 1.2 ⫾ 1.0 2⫾1 0 2 (28) 1 (14) 83 25 ⫾ 17
16 (3%) 58.7 ⫾ 12 31.8 ⫾ 5.1 3 (2–3) 0 (0–2) 3.1 ⫾ 1.1 345 ⫾ 416 29.2 ⫾ 13.7 3.9 ⫾ 1.5 31 ⫾ 23 3.6 ⫾ 2.7 2.1 ⫾ 1.9 2.3 ⫾ 1.3 1 (6) 5 (25) 1 (6) 83 27 ⫾ 20
0.003 0.04 0.58 0.16 0.05 0.13 0.44 0.91 0.65 0.11 0.38 0.42 0.78 0.38 0.80 0.52 0.99† –
1.7 ⫾ 0.2 1.8 ⫾ 0.2 12.8
0.9 ⫾ 0.1 1.4 ⫾ 0.6 50.8
⬍0.001 0.1 0.11
41.2 ⫾ 7.6 36.2 ⫾ 10.2 12
92.8 ⫾ 19.2 70.1 ⫾ 16.7 23
⬍0.001 ⬍0.001 0.20
ASA, American Society of Anesthesiology; BMI, body mass index; CCI, Charlson Comorbidity Index; GFR, glomerular filtration rate. * Median (range). † Log rank.
COMMENT In the management of patients with a small renal tumor and chronic renal insufficiency, preservation of nephron mass is imperative. During partial nephrectomy, warm ischemia may be more deleterious to the function of a baseline compromised kidney vis-à-vis a normal kidney. To our knowledge, no prior report, open or laparoscopic, has specifically focused on outcomes of partial nephrectomy with hilar clamping in patients with preexisting renal dysfunction. Salient findings of our study are as follows. Patients with preoperative renal insufficiency were older, less healthy, and deemed to have higher anesthetic risk (P ⬍0.001). This group also had larger tumor size and a higher percentage of solitary kidneys and bilateral tumors. Despite the above, intraoperative parameters, postoperative outcomes, overall complications, and histopathologic data were comparable between groups. Of note, duration of hilar clamping (warm ischemia time) and amount of kidney parenchyma excised (specimen weight) were also similar between groups. Although the preoperative, and consequently the postoperative, renal function was expectedly inferior in group I patients, the percent postoperative reduction in renal function appeared to be similar between groups. Within group I, subgroup outcomes analysis of patients with baseline serum creatinine 1.5 to 1.9 mg/dL versus those with serum creatinine 2 mg/dL or greater also revealed comparable deterioration in renal function. Fi1046
nally, among patients with baseline renal dysfunction, those aged greater than 70 years and undergoing warm ischemia more than 30 minutes had the greatest postoperative deterioration of renal function (Table 4). These data indicate that older patients (greater than 70 years) with longer warm ischemia time (more than 30 minutes) are at risk for postoperative renal function deterioration after LPN with hilar clamping. This high-risk subgroup of patients should preferably be treated with alternate nephron-sparing strategies with use of hypothermia, or probe ablative therapies such as cryoablation or radiofrequency ablation. Renal functional outcomes after partial nephrectomy are documented in the literature. In patients with a normal contralateral kidney, open partial nephrectomy resulted in a lower incidence of chronic renal insufficiency (defined as serum creatinine greater than 2 mg/dL) compared with radical nephrectomy (11.6% versus 22.4%; relative risk, 3.7).8 Similarly, in patients with a small (4 cm or less) renal tumor and normal contralateral kidney, postoperative serum creatinine was lower after open partial versus radical nephrectomy (1.0 versus 1.5 mg/dL; P ⬍0.001).9 Thompson et al. documented chronic renal insufficiency/renal failure in 14.6% of historic and 8.1% of contemporary patients after open partial nephrectomy.10 In Desai’s functional analysis of our 179 patients, although no clinically apparent sequelae were noted with a warm ischemia time of up to 30 minutes, advancing age (greater than 70 years) and preexisting azotemia inUROLOGY 71 (6), 2008
Table 4. Renal functional outcomes between group I (abnormal renal function) and group II (normal renal function) and impact of warm ischemia time and patient age on ultimate renal function Group I Serum creatinine (mg/dL) Preoperative Postoperative % Change Estimated GFR* (mL/min) Preoperative Postoperative % Change Dialysis Temporary Permanent
Serum creatinine Preoperative Postoperative % Increase GFR Preoperative Postoperative % Decrease
Group II
P-Value
1.9 ⫾ 0.4 2.2 ⫾ 0.8 20% (95% CI, 12.7 to 29.2)
0.9 ⫾ 0.2 1.1 ⫾ 0.6 21% (95% CI, 17.9 to 24)
⬍0.001 ⬍0.001 0.99
37.7 ⫾ 9.1 31 ⫾ 9.7 16% (95% CI, ⫺22 to ⫺11) 5 (10%) 3 (6%) 2 (4%)
85.1 ⫾ 18.9 70.3 ⫾ 19.8 16% (95% CI, ⫺18.2 to ⫺13.9) 3 (0.6%) 2 (0.4%) 1 (0.2%)
⬍0.001 ⬍0.001 0.89 ⬍0.001 ⬍0.001 ⬍0.001
Warm Ischemia Time ⬍30 min Subgroup Ia Subgroup Ib (Age ⬍70 yr) (Age ⬎70 yr) P-Value
Warm Ischemia Time ⬎30 min Subgroup Ic Subgroup Id (Age ⬍70 yr) (Age ⬎70 yr) P-Value
2.0 ⫾ 0.5 2.1 ⫾ 0.4 10.2 ⫾ 11.9†
1.7 ⫾ 0.3 2.2 ⫾ 0.7 17.7 ⫾ 26.6
0.12 0.83 0.34
1.8 ⫾ 0.3 2.1 ⫾ 0.9 16.8 ⫾ 24.3
32 ⫾ 10 30 ⫾ 8 11.7 ⫾ 16.4‡
38 ⫾ 7 32 ⫾ 12 14 ⫾ 28.6
0.16 0.63 0.73
40 ⫾ 7 36 ⫾ 8 9.3 ⫾ 23
1.7 ⫾ 0.4 2.2 ⫾ 0.6 25.4 ⫾ 18†
0.66 0.68 0.54
40 ⫾ 7 29 ⫾ 7 25.6 ⫾ 12.8‡
0.88 0.13 0.13
Abbreviations as in previous tables. * Glomerular filtration rate ⫽ [[140 ⫺ age (yr)] ⫻ weight (kg)]/[72 ⫻ serum Cr (mg/dL)] (multiply by 0.85 for women). Group I (n ⫽ 48): Patients with baseline serum creatinine greater than 1.5 mg/dL. Subgroup Ia (n ⫽ 13): Within group I, patients aged less than 70 years with warm ischemia time less than 30 minutes. Subgroup Ib (n ⫽ 12): Within group I, patients aged greater than 70 years with warm ischemia time less than 30 minutes. Subgroup Ic (n ⫽ 12): Within group I, patients aged less than 70 years with warm ischemia time greater than 30 minutes. Subgroup Id (n ⫽ 11): Within group I, patients aged greater than 70 years with warm ischemia time greater than 30 minutes. † P-Value (subgroup Ia versus Id) ⫽ 0.02. ‡ P-Value (subgroup Ia versus Id) ⫽ 0.03.
creased the risk of postoperative renal dysfunction, particularly when the warm ischemia time exceeded 30 minutes.11 In the study recently published by Kobayashi et al., the authors confirmed this result using scintigraphic renal analysis.12 In 22 patients with a solitary kidney, the reduction of renal function (approximately 30% increase in serum creatinine) appeared commensurate with the amount of renal parenchyma excised (approximately 23%).13 In the current study, overall survival was inferior in group I, which is not surprising given the higher prevalence of preexisting comorbidities. However, estimated 5-year cancer-specific survival was similar between groups (100% versus 98%; P ⫽ 0.65). We recognize the limitations of our study. Although collected prospectively, the data were analyzed retrospectively. Serum creatinine is a less than ideal parameter to investigate renal function. Renal scan data were not available uniformly, precluding postoperative determination of differential function of the operated kidney. Similarly, data regarding 24-hour urinary protein excretion are lacking, which would add to our understanding of the impact of warm ischemia on the compromised kidney. The strength of this report is the large number of patients with abnormal renal function undergoing LPN with relatively long functional follow-up. UROLOGY 71 (6), 2008
Certain considerations are pertinent when performing LPN in patients with renal dysfunction. Investigation and optimization of preoperative cardiopulmonary status are essential. Renal perfusion and diuresis are maximized by judicious administration of intravenous fluids and diuretics. In our study, despite comparable intravenous fluid administration, intraoperative urine output was significantly lesser in the patients with renal dysfunction. We typically administer 12.5 g of mannitol at the time of hilar dissection and a repeat 12.5 g mannitol plus 20 mg of furosemide 2 to 3 minutes before hilar unclamping. Hilar control is efficiently achieved by en bloc clamping. Every effort is made to minimize renal ischemia time. Preplanning of maneuvers for tumor excision and renal repair, an experienced team, and complete comfort in the laparoscopic environment are essential in this regard.
CONCLUSION Older patients with compromised renal function and warm ischemia time greater than 30 minutes are at high risk for renal dysfunction after LPN with hilar clamping. Alternate nephron-sparing methods including hypothermia or nonclamping probe-ablation should be considered in this patient subset. 1047
References 1. Chow WH, Devesa SS, Warren JL, et al: Rising incidence of renal cell cancer in the United States. JAMA 281: 1628-1631, 1999. 2. Culleton BF, Larson MG, Evans JC, et al: Prevalence and correlates of elevated serum creatinine levels: the Framingham Heart Study. Arch Intern Med 159: 1785-1790, 1999. 3. Iseki K, Ikemiya Y, and Fukiyama K: Risk factors of end-stage renal disease and serum creatinine in a community-based mass screening. Kidney Int 51: 850-854, 1997. 4. Becker F, Siemer S, Humke U, et al: Elective nephron sparing surgery should become standard treatment for small unilateral renal cell carcinoma: long-term survival data of 216 patients. Eur Urol 49: 308-313, 2006. 5. Lane BR, and Gill IS: Five-year outcomes of laparoscopic partial nephrectomy. J Urol 177: 70-74, 2007. 6. Gill IS, Desai MM, Kaouk JH, et al: Laparoscopic partial nephrectomy for renal tumor: duplicating open surgical techniques. J Urol 167: 469-474, 2002. 7. Haber GP, and Gill IS: Laparoscopic partial nephrectomy: contemporary technique and outcomes. Eur Urol 49: 660-665, 2006.
1048
8. Lau WK, Blute ML, Weaver AL, et al: Matched comparison of radical nephrectomy vs. nephron-sparing surgery in patients with unilateral renal cell carcinoma and a normal contralateral kidney. Mayo Clin Proc 75: 1236-1242, 2000. 9. McKiernan J, Simmons R, Katz J, et al: Natural history of chronic renal insufficiency after partial and radical nephrectomy. Urology 59: 816-820, 2002. 10. Thompson RH, Leibovich BC, Lohse CM, et al: Complications of contemporary open nephron sparing surgery: a single institution experience. J Urol 174: 855-858, 2005. 11. Desai MM, Gill IS, Ramani AP, et al: The impact of warm ischaemia on renal function after laparoscopic partial nephrectomy. BJU Int 95: 377-383, 2005. 12. Kobayashi Y, Usui Y, Shima M, et al: Evaluation of renal function after laparoscopic partial nephrectomy with renal scintigraphy using 99mtechnetium-mercaptoacetyltriglycine. Int J Urol 13: 13711374, 2006. 13. Gill IS, Colombo JR Jr, Moinzadeh A, et al: Laparoscopic partial nephrectomy in solitary kidney. J Urol 175: 454-458, 2006.
UROLOGY 71 (6), 2008