Our findings show that 26% of patients with a solitary, small, renal cortical tumour (<4 cm) and two normally functioning kidneys have pre-existing chronic kidney disease (GFR <60 mL/min per 1·73 m2). This study also shows that the risk of new onset of chronic kidney disease is significantly greater in patients undergoing radical nephrectomy than in those undergoing partial nephrectomy for treatment of small, renal cortical tumours.
In 2006, more than 35 000 patients will develop renal cortical tumours in the USA, with a rising incidence of about 3% per year.24,25
Since more than 60% of newly diagnosed tumours are 4 cm or less in size, more than 20 000 patients every year will have tumours amenable to partial nephrectomy based on size criteria alone.4
Since data indicate no significant difference in cancer-specific survival between patients undergoing partial nephrectomy for tumours sized 7 cm or less and those undergoing surgery for tumours less than 4 cm, the actual number of patients eligible for the procedure could be more than expected.26,27
Our findings are important because an overwhelmingly disproportionate number of patients with small, renal cortical tumours are treated with radical nephrectomy instead of partial nephrectomy.8-10
Although experienced surgeons report similar complication rates and outcomes for both the procedures,28,29
the partial approach can be technically challenging and might be associated with a greater risk of complications, especially if done laparoscopically.29
In our series of open partial and radical nephrectomies,28
the frequency of complications did not differ between operation type when accounting for multiple variables. We did not record any perioperative mortalities due to technical complications from partial nephrectomy, and the most common complication after the procedure were urinary fistulas (6%), none of which needed re-operation.28
Nevertheless, the potential complexity of partial nephrectomy—along with increasing use of laparoscopic radical nephrectomy,7,30
which is much less difficult than partial nephrectomy—could contribute to the high number of radical nephrectomies being done for small renal cortical tumours.
However, the overuse of radical nephrectomy for small, renal cortical tumours is probably due to the widespread misconception that chronic kidney disease after radical nephrectomy is not a major concern in patients with two functioning kidneys and a normal preoperative concentration of serum creatinine. Outcome data from transplantation studies31-33
have long supported this notion, since donors undergoing nephrectomy do not have higher rates of decreased kidney function, kidney failure needing dialysis, or death.
However, our data show that unlike kidney donors, patients with small, renal cortical tumours are at a significantly higher risk of developing chronic kidney disease after radical nephrectomy than after partial nephrectomy. Even with other important variables accounted for, such as age at time of surgery, preoperative estimated GFR, Charlson-Romano index, and presence of hypertension, patients undergoing radical nephrectomy are at a significantly increased risk of chronic kidney disease. Despite differences in follow-up between surgery groups because of the increased proportion of partial nephrectomies over time, proportional hazards assumptions were met (p=0·5 and p=0·6 for events of GFR <60 and GFR <45 mL/min per 1·73 m2, respectively).
Two factors might explain the increased risk of chronic kidney disease after radical nephrectomy in our patients compared with kidney donors: the GFRs recorded in our study might have been underestimated because of uncalibrated serum creatinine assays; and the baseline estimated GFRs are significantly lower in patients with renal cortical tumours than in those undergoing donor nephrectomy. Some studies34,35
have suggested underestimation of GFR in patients without kidney disease, by estimating equations derived from studies of patients with chronic kidney disease. This underestimation seems to be greater in studies that did not calibrate the serum creatinine assay to the laboratory from which the estimating equation was derived.19
Although our study might have overestimated the true number of patients with chronic kidney disease using an estimated GFR cutoff of lower than 60 mL/min per 1·73 m2
, the use of estimated GFR lower than 45 mL/min per 1·73 m2
as an additional outcome is most likely to identify patients with chronic kidney disease.
The baseline estimated GFR of our entire cohort of patients (69 mL/min per 1·73 m2
) is substantially lower than in patients from published donor nephrectomy series (92–103 mL/min per 1·73 m2
A comparison with age-matched patients from the third National Health and Nutrition Examination Survey (NHANES III)39
also reported a median baseline GFR that was 30% greater than that in our patients. This disparity in the baseline GFRs can be attributed to differences in patient age at the time of nephrectomy as well as frequency of pre-existing comorbidities that affect kidney function. In studies of the outcomes of kidney donors, the reported mean ages at time of kidney donation were often younger than 50 years.36,38,40
In our series, the median age at radical nephrectomy was 58 years (IQR 50–67). With a conservative estimation of GFR reduction over time (1 mL/min per 1·73 m2
this finding alone accounts for a 10% reduction in the baseline GFR of patients with renal cortical tumours. The increased frequency of risk factors for chronic kidney disease, such as hypertension, diabetes mellitus, and smoking, probably explains why about 25% of patients with small, renal cortical tumours also have pre-existing chronic kidney disease and why a significant portion of the remaining 75% are at risk after radical nephrectomy. Until now, most urological studies have used serum creatinine instead of estimated GFR to measure kidney function,11,12
which could explain why the lower renal function at baseline of patients with renal cortical tumours has largely gone unnoticed.
Our results raise serious concerns regarding the lasting effects of radical nephrectomy on the length and quality of life of patients. Since the cancer-specific survival for patients with small, renal cortical tumours is greater than 90% across all histological subtypes,4,41
these patients are susceptible to developing long-term sequelae from their treatment. Several studies16-18
have shown an independent and graded association between decreased estimated GFR and substantial comorbidity, increased admissions, and increased cardiac-related and non-cardiac-related deaths. Patients undergoing radical nephrectomy have a greater than 35% chance of developing a GFR lower than 45 mL/min per 1·73 m2
within 3 years of surgery, theoretically placing them at risk for these complications. Since patients with renal cortical tumours are at higher lifetime risk for contralateral recurrences and since 20% of small, renal cortical tumours are indolent,42
the routine use of radical nephrectomy for these tumours is both unnecessary and unjustified.
Our study had some limitations. As a retrospective study, patients were not randomly assigned to a surgical procedure, which meant that the choice of surgery might have been biased by the surgeons' preference based on the preoperative condition of the patient. However, we showed that the cohorts were well balanced before surgery. Furthermore, randomisation in a prospective study would be difficult to implement at our institution, with the knowledge that patients would have no oncological benefit and a potentially significant risk of chronic kidney disease. Another limitation was GFR estimation. As previously mentioned, formulas based on serum creatinine concentrations vary in accuracy in different patient groups. We chose to use the abbreviated MDRD study equation, widely used in other studies to show associations between estimated GFR, comorbidity, and death.16,18,19
Although this formula is generally accepted as a more accurate method to estimate GFR, the reduction in baseline and follow-up estimated GFRs seen in our cohort could be partly due to formulaic inadequacies of the estimation of GFR as well as the use of uncalibrated serum creatinine values.
Since the mechanism by which decreased GFR increases the risk of cardiovascular disease and death has yet to be established, the ramifications of chronic kidney disease in these patients remain unknown. Longitudinal analysis of nationwide databases similar to the SEER registry is needed to establish whether the iatrogenic and abrupt onset of chronic kidney disease after surgery places patients at risk for associated complications, such as cardiovascular disease and death.
Our data indicate that many patients are at risk for chronic kidney disease, after unnecessary use of radical nephrectomy for the treatment of small, renal cortical tumours. Therefore, these findings have important and immediate implications on the contemporary management of these tumours. We believe that standardised preoperative GFR estimates should be an integral part of the decision algorithm during planning of the surgical strategy for patients with renal cortical tumours, irrespective of tumour size. Treatment options that provide equivalent oncological results and preserve kidney function outcomes might also replace radical nephrectomy as the gold standard treatment for small, renal cortical tumours. Based on the increasing number of studies showing long-term deleterious effects of chronic kidney disease, doctors should be aware that the preferred treatment for small, renal cortical tumours could have a substantial effect on the quality and length of survivorship of these patients.