Percutaneous Radiofrequency Ablation Does Not Affect Glomerular Filtration Rate

Abstract

Purpose:

To study short- and intermediate-term global renal function in patients undergoing a single percutaneous radiofrequency ablation (pRFA) for a solitary renal parenchymal tumor.

Materials and Methods:

We reviewed the records of 62 patients who underwent a single pRFA for solitary renal parenchymal tumor. We used the abbreviated Modified Diet for Renal Disease equation to calculate baseline, 1-month, and 1-year glomerular filtration rate (GFR). We defined normal as >60, moderately diminished as 45–60, and severely diminished GFR as <45 cc/minute/1.73 m². We used the Wilcoxon paired rank sum method to compare 1-month and 1-year GFR to baseline. We fit a linear regression model to test the association of lesion size to GFR controlling for lesion location and baseline GFR.

Results:

There was no difference in GFR from baseline at 1 month or 1 year (55 vs. 58 cc/minute/1.73 m², p = 0.24 and 55 vs. 57 cc/minute/1.73 m², p = 0.8, respectively). Tumor size did not affect GFR at 1 month or 1 year after controlling for lesion location and baseline GFR.

Conclusions:

A single application of pRFA does not affect GFR in the short or intermediate term.

Introduction

T he use of diagnostic abdominal imaging has dramatically increased over the last two decades, leading to increased detection of small renal parenchymal tumors (RPTs).^1,2 Partial nephrectomy (PN) or radical nephrectomy (RN) are the standard treatments for T1 lesions, with 5-year disease-free rates exceeding 90%.^3
–5 However, comorbidity may limit the applicability of extirpative treatment in a significant portion of patients, and there are no widely accepted surveillance protocols.⁶

Recently, some have questioned the global health impact of extirpative renal surgery. Huang and colleagues⁷ reported a 11.8-fold increase in the risk of developing severe chronic kidney disease in patients who have undergone RN compared with PN. Thompson et al⁸ reported a decreased overall survival in patients younger than 65 who had undergone RN compared with PN for T1a RPTs. These observations are supported by several large series reporting an association of cardiac and noncardiac morbidity and mortality in patients with diminished renal capacity.^9

–12 Therefore, any therapeutic intervention should have the goals of oncologic control and optimization of postintervention renal reserve.

Percutaneous radiofrequency ablation (pRFA) is a procedure that involves passing a probe through the skin into the renal lesion and thermally ablating the lesion using imaging guidance. This approach does not require a general or regional anesthetic, is associated with little peri-procedural morbidity, and is usually performed on an outpatient basis.¹³ Although use of pRFA is increasing, long-term oncologic efficacy data are incomplete but evolving; therefore, prudent patient selection is crucial.

The aim of this study was to determine the effect of a single pRFA of a solitary RPT on global renal function, as measured by estimated glomerular filtration rate (GFR) over a 1-year period and to determine whether tumor size or location affects this outcome.

Materials and Methods

Before initiating this analysis, the Institutional Review Board approved this study. We queried our prospectively collected pRFA database for all patients who had renal RFA between May 2000 and December 2007. We conducted a chart review to obtain missing data. To elucidate the effect of a single treatment with pRFA, we excluded patients with regional or distant spread, multiple lesions, and those who required multiple pRFA sessions (including those who had pRFA for recurrent or residual disease). In addition, patients with end-stage renal disease requiring dialysis at baseline were excluded to avoid introducing bias. Only patients who had been followed for a minimum of 1 year and who had complete GFR data at baseline, 1 month, and 1 year were included in the final analysis.

All patients in this study, except one, had an enhancing RPT on axial imaging. They were seen by a urologist, and treatment options, including observation, PN, RN, and thermal ablation, were discussed before being referred to interventional radiology for treatment. Patients were selected for pRFA according to their desire for an intervention and the surgeon's assessment that the surgical risk was excessive. All patients were seen in the Interventional Radiology clinic, where they were counseled about the risks, benefits, and efficacy of pRFA. All patients signed informed consent before treatment.

In patients with central lesions or those in proximity to the collecting system or ureter, an end-hole stent was placed immediately before pRFA to cool the ureter and collecting system with pyeloperfusion of chilled D5W during the ablation. Preablation biopsy was routinely performed at the time of pRFA. Both a fine-needle aspirate for cytology and a core biopsy for histology were obtained. A cytotechnologist reviewed all specimens in the procedure room to determine their adequacy for diagnosis. The technique used for pRFA has been previously described.¹³ The urology team conducted the remainder of follow-up, which consisted of basic serum electrolytes; renal imaging with ultrasonography, magnetic resonance imaging, or computed tomography; chest X-ray; and interval history and physical at 1, 6, and 12 months postablation.

Statistics

GFR was estimated using the abbreviated Modified Diet for Renal Disease equation. We used standard descriptive methods to describe our cohort. For descriptive purposes, we defined normal GFR as >60 cc/minute/1.73 m², moderately diminished as 45–60 cc/minute/1.73 m², and severe as <45 cc/minute/1.73 m². We defined a nondiagnostic biopsy as having inadequate tissue for a specific diagnosis or containing only normal renal parenchyma. For comparison to baseline, GFR was considered as a continuous variable using the matched Wilcoxon sign rank method. We fit a multivariable linear regression model to test for lesion size for association with GFR at 1 month and 1 year while controlling for baseline GFR, and tumor location. For this purpose, we re-reviewed the preablation abdominal imaging in all patients, and categorized each tumor as exophytic versus not exophytic. We defined exophytic as any tumor with >25% of tumor circumference in contact with perirenal fat.¹⁴ All statistics were performed using STATA (College Station).

Results

A total of 62 patients with a median age of 71 (interquartile range [IQR]: 73, 78) and a median follow-up of 24 months (IQR: 16, 38) met our selection criteria and had complete data available. The median tumor size was 1.9 cm (range, 0.8–5.6). All lesions were stage T1, based on imaging findings. Median baseline GFR was 55 cc/minute/1.73 m² (IQR 44, 70), and 27 (43%), 19 (31%), and 16 (26%) patients had normal, moderately diminished, and severely diminished GFR, respectively. Baseline characteristics are tabulated in Table 1.

Table 1.

Tumor and Patient Characteristics

Cohort characteristics, n = 62
Age, median (IQR)	70	(63, 78)
Size (cm), median (IQR)	1.9	(1.4, 2.7)
Side (%)
Left	35	(56)
Right	27	(44)
Stage (%)
T1a	58	(94)
T1b	4	(6)
Race (%)
White	50	(81)
African American	11	(18)
Indian	1	(1)
Baseline GFR (%)
>60	27	(44)
45–60	19	(31)
<45	16	(25)
Serum creatinine, median (IQR)
Baseline	1.25	(1.0–1.6)
1 month	1.20	(1.0–1.7)
1 year	1.20	(1.0–1.7)
Sex (%)
Male	38	(61)
Female	24	(39)
Location of tumor (%)
Exophytic	45	(73)
Parenchymal	12	(19)
Endophytic	2	(3)
Mixed	3	(5)

GFR = glomerular filtration rate; IQR = interquartile range.

A total of 61 (98%) patients had a preablation biopsy. Of these, 14 (23%) were nondiagnostic. Forty-two (68%) were unequivocally malignant; 4 (7%) and 1 (2%) were interpreted as oncocytoma and angiomyolipoma, respectively (Table 2).

Table 2.

Biopsy Results

Biopsy histology	Number	%
Renal cell carcinoma	42	(68)
Nondiagnostic	9	(15)
Negative	5	(8)
Oncocytoma	4	(7)
Angiomyolipoma	1	(1)
Not done	1	(1)

At 1 month and 1 year postablation the median GFR was 58 cc/minute/1.73 m² (42, 72) and 57 cc/minute/1.73 m² (42, 75), respectively. A total of 15% of patients experienced a categorical diminution of renal function, defined as recharacterization from normal to moderately or severely diminished or from moderately diminished to severely diminished, at 1 year of follow-up. Nineteen percent actually had a categorical improvement in renal function at 1 year. Median GFR did not change significantly from baseline at 1 month (55 vs. 58 cc/minute/1.73 m², p = 0.24) or at 1 year (55 vs. 57 cc/minute/1.73 m², p = 0.8). Tumor size did not impact GFR at 1 month or 1 year when baseline GFR and tumor location (exophytic vs. not exophytic) were controlled (coefficient − 0.36, p = 0.8, and coefficient − 1.9, p = 4, respectively; Table 3).

Table 3.

Regression Analysis: Effect of Tumor Size and Location on Glomerular Filtration Rate

GFR 1 month	Coefficient	95% confidence interval	p-Value
Tumor size	−0.4	−3.1, 2.4	0.8
Exophytic location^a	−2.1	−8.7, –4.5	0.5
Baseline GFR	0.9	0.8, 1.0	<0.001
GFR 1 year
Tumor size	−1.9	−6.1, 2.2	0.4
Exophytic location^a	−0.7	−10.6, 9.2	0.001
Baseline GFR	0.7	0.6, 0.8	<0.001

Referent: Nonexophytic.

Discussion

The current study indicates that a single pRFA has minimal impact on global renal function in the short and intermediate term. These results are important because most patients in this cohort were deemed unfit or poorly suited for extirpative surgery, and these findings contribute to our understanding of the impact of pRFA on a highly comorbid population.

General health and overall survival are dependent upon renal function. As GFR decreases, the risk for cardiovascular and noncardiovascular morbidity and mortality increases.^9
–11 Even modest diminution of renal capacity is detrimental; most patients die from other causes before renal transplantation or dialysis become necessary.¹⁵ Importantly, the National Health and Nutrition Examination Survey data suggest that GFR is declining across the general population with time.¹⁶ This has also been observed in patients undergoing extirpative renal surgery.¹⁷ Thus, treatment for small renal lesions of uncertain significance should attempt to minimize the negative impact to global renal function, particularly in patients who already have chronic kidney disease as the majority of cohort did.

Surgical series have demonstrated that PN and RN negatively impact GFR. The Memorial Sloan Kettering group⁷ showed that patients who were treated with RN were 11.8-fold more likely to develop severely diminished GFR than those who had PN. In a follow-up study, the group found GFR independently linked to overall survival after extirpative surgery for RPTs.¹⁷ Miller and colleagues¹⁸ reported that 60% of patients experienced a cardiac event during follow-up after renal extirpative surgery in the Surveillance Epidemiology and End Results-Medicare population. Huang and coworkers¹⁹ confirmed the observation that patients who had undergone RN for small renal masses had inferior overall survival.

Renal function after PN does not seem to be related to tumor location once tumor size, patient age, and baseline GFR are considered.²⁰ However, after PN, GFR does seem to be diminished at least in the short and intermediate term.^5,21,22 The current trend toward minimally invasive surgery also presents obstacles to modulate the ischemia since achieving effective cold ischemia, minimizing ischemia time, and performing PN without clamping the hilum may be very difficult or impossible in the laparoscopic or robotic setting.⁵ Although laparoscopic PN is associated with less pain, less blood loss, and shorter hospital stay, patients with pulmonary comorbidity may not tolerate pneumoperitoneum. Similarly, those with multiple previous abdominal surgeries may require long operative times, which may be associated with higher complications rates.⁵

Complications after pRFA occur in 3%–8% of patients.²³ Common complications include bleeding, infection, pneumothorax, and ureteral stricture. Zagoria and coworkers¹³ previously reported the complications associated with our initial experience at Wake Forest University. Review of our cohort revealed two (3%) complications. One patient developed a proximal ureteral stricture, which is being observed. The second patient had a large retroperitoneal hematoma, which exerted mass effect on the kidney. Despite percutaneous drainage, he developed acute renal failure and ultimately became hemodialysis dependent. We also had 9 (8%) small, clinically insignificant perinephric hematomas seen on post-RFA imaging. Complications from PN have been reported to be 17%–20%,^5,24 with laparoscopic PN having a significantly higher proportion of complications requiring invasive intervention.

The long-term oncologic efficacy of pRFA has not been established. Intermediate results have been mixed. Zagoria and coworkers¹³ reported a 100% disease-free interval in patients treated with a single application of pRFA for lesions smaller than 3.7 cm with 14-month mean follow-up. However, recurrence occurred in 47% of patients with larger lesions. They were able to salvage 23% with one additional ablation. Hui et al²³ conducted a meta-analysis of 46 series and found that a single percutaneous ablation with either cryoablation or RFA was less effective than laparoscopic ablation (87% vs. 94%) but that with a second ablation the disease-free rate was not different (92% vs. 94%). Further, they reported that the complication rate for percutaneous ablation was 3% compared with 7% for laparoscopic ablation. However, Kunkle and colleagues⁶ reported a 18.23-fold increase in relative risk of local recurrence for RFA compared with PN in a meta-analysis of 99 studies, but they found no difference in metastatic progression. These results are encouraging if viewed from the vantage point of a poor surgical candidate with a small RPT.

In the current series, we found no significant difference between baseline, 1-month, and 1-year GFR after a single session of pRFA for small renal lesions. Our data do show that 15% of the cohort did experience a categorical decrease in renal function. However, 19% actually had a categorical improvement. These data should be interpreted cautiously. These categorical shifts are likely a result of using artificial cut-offs rather than relying on continuous data. We used this method for illustrative purposes only, not for statistical analysis. The Modified Diet for Renal Disease equation may underestimate renal function in young and healthy individuals,²⁵ and it is highly dependent upon creatinine levels, which may vary according to many factors independent of the number of functioning nephrons. Our short and intermediate GFR data compare favorably with the results reported in the PN literature.^5,21,22 The 1-month and 1-year GFR were not associated with the lesion size, contrary to what has been shown in other series.²⁰ The difference is likely related to the relatively small size of these lesions and narrow range of sizes treated in this study.

Sixty-one (98%) of the patients in this cohort were biopsied before pRFA. The high nondiagnostic rate of 23% (negative and nondiagnostic specimens) underscores the difficulty in risk stratification for these small RPTs. These results confirm the observations of others. The Mayo Clinic group²⁶ reported a 20% nondiagnostic rate with a sensitivity of 81%, specificity of 60%, and accuracy of 77% in patients who underwent CT-guided biopsy before RN. Further, an enhancing renal neoplasm on CT or MRI has been considered by most urologists to be a sufficient indication for surgery because about 80% of such lesions prove to be renal cell carcinoma (RCC).²⁷ Since a significant portion of small RPTs will have indolent or benign pathology,⁴ it would be ideal to have accurate and reliable biopsy data to help risk-stratify patients for observation or intervention. Unfortunately, this is not yet reality. Therefore, even in the face of a nondiagnostic preliminary cytohistologic report, we are inclined to proceed with RFA.

This series has several shortcomings. It is a retrospective study and therefore is associated with all of the shortcomings of retrospective studies. This is a relatively small series from a highly selected group of patients. We were unable to control for other factors that may affect renal function such as comorbidites and use of nephrotoxic drugs. Similar studies of larger cohorts, ideally from multiple institutions, are needed to validate our observations. These results are from pRFA and should not be extrapolated to laparoscopic radiofrequency ablation or cryoablation, as those procedures include more tissue manipulation and may be associated with a different toxicity profile. Finally, the patients in this cohort were all treated with a single pRFA; subsequent treatments may impact GFR more significantly; therefore, caution should be exercised in broadly interpreting these results.

As the population continues to age, urologists can expect to see more patients with complex medical and surgical problems who have small RPTs. In patients who are suboptimal surgical candidates, pRFA may provide a safe alternative to extirpative surgery.

Conclusions

A single pRFA does not negatively affect global renal function in the short and intermediate term. This treatment modality may represent a reasonable treatment option for those patients with small renal cortical tumors who are not surgical candidates.

Footnotes

Disclosure Statement

RJZ-Research grant from Covidien Inc.

Abbreviations Used

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