Saving as Many Nephrons as Possible

By Steven C. Campbell, MD, PhD

One of the primary goals of partial nephrectomy (PN) is to preserve as much renal function as possible. This is particularly important in patients with imperative indications such as a solitary kidney or pre-existing chronic kidney disease (CKD).

Factors that can influence ultimate renal function after PN include the quality of the nephrons prior to surgery, the quantity of nephrons preserved, and the type (warm versus cold) and duration of ischemia.

A Flawed View of Ischemia Time’s Significance

The quality of the nephrons is determined by the patient’s age and the presence of comorbidities such as diabetes, and is essentially nonmodifiable. Early studies reported an association between warm ischemia time and increased incidence of CKD, and a cause-and-effect relationship was presumed, expressed by the catchphrase “every minute counts.”

However, these studies were inherently flawed because they failed to incorporate all the potentially relevant contributing factors, most notably, the quantity factor, which is the volume of nephron mass preserved by the procedure. When this factor is included in the analyses, ischemia time loses all significance unless it is warm and prolonged (> 25 minutes).

Stated more simply, these studies have shown that almost all preserved nephrons recover completely from the ischemic insult as long as limited warm ischemia or hypothermia is applied. How can we optimize the quantity factor — the number of nephrons saved by the procedure?

Studying the Impact of Surgical Precision on PN Outcomes

The number of nephrons saved during PN is determined by the precision with which we excise the tumor and reconstruct the kidney. Some have argued that this precision is also a nonmodifiable factor because it is largely influenced by tumor size and location. Based on this line of reasoning, functional outcomes after PN would be mostly out of our control as surgeons, as long as we avoid extended warm ischemia. But is this really true?

We recently studied the precision of tumor excision and reconstruction in a series of 122 patients with conventionally clamped PNs at our center, including a representative mix of cases with cold ischemia (N = 50) and warm ischemia (N = 72). Forty-five patients (37 percent) had a solitary kidney.

Volumetric computed tomography (CT) scans were used to measure the volume of vascularized normal parenchyma before and four to 12 months after surgery as previously described. We presumed that an “ideal PN” would be associated with the loss of an approximate 5 mm rim of normal parenchyma due to tumor excision (some parenchyma is removed along with the tumor to avoid a positive margin) as well as devascularization of a modicum of adjacent parenchyma (related to capsular closure to minimize the risk of postoperative leak and bleeding).

Figure 1 illustrates our estimate of the amount of parenchyma and tumor that would be lost during PN for an anteriorly located, intrinsic tumor, and includes some radially located tissue that would be compromised in this setting. After subtracting the volume of the tumor, the amount of parenchyma that would be lost with an ideal PN was then estimated. We defined precision of tumor excision and reconstruction as the amount of vascularized parenchyma actually saved divided by the amount that would have been saved with an ideal PN.

Figure1. Volumetric CT to measure the amount of parenchyma that would be lost during an ideal PN for an anteriorly located, intrinsic tumor. The kidney is viewed from anterior and medial aspects. Summation of areas at 3 mm intervals is utilized to obtain volume estimates as previously described.

In our series, the median value for surgical precision was 93 percent, demonstrating that most PNs approximated the best-case scenario in terms of preservation of nephron mass. On univariate and multivariate analysis, the only factor that correlated with surgical precision was the presence of a solitary kidney, while tumor size and complexity, type and duration of ischemia, and other factors failed to correlate.

Surgical Precision Is Modifiable and Important

Our data suggest that precision was highest when it was at a premium (i.e., in patients with a solitary kidney), likely related to the recognized need to preserve as much renal parenchyma as possible given the absence of a contralateral kidney. In the end, surgical precision appears to be a modifiable factor, and it appears to be the most important factor for determining ultimate renal function after PN.

Our perspective is that high-quality preoperative imaging, intraoperative ultrasonography and operating within a bloodless field can all facilitate surgical precision.

Efforts to optimize surgical precision will be important moving forward. They could include energy-based resection and hemostatic agents that might preclude the need for capsular reconstruction; further improvements in perioperative imaging; and selective utilization of tumor enucleation.

Dr. Campbell is Vice Chair of Cleveland Clinic Glickman Urological & Kidney Institute’s Department of Urology, Director of the Urology Residency Program, Associate Director of Graduate Medical Education and Professor of Surgery at Cleveland Clinic Lerner College of Medicine. He holds the Eric A. Klein Endowed Chair in Urologic Oncology and Education.