Fig. 10.1
Bidirectional interactions between CKD and RCC
For those patients with mild CKD or no evidence of CKD prior to the diagnosis of RCC, the surgical procedure will have important effects on long-term renal function. Most studies support the fact that there will be clear differences in resultant glomerular filtration rate (GFR) between partial and radical nephrectomies, both in the short- and long-term. For example, Huang et al. reported that the probability of being free from a GFR < 60 ml/min/1.73 m2 at 5 years post procedure was 67 % and 23 % for partial and complete nephrectomy, respectively with no difference in oncologic efficacy [27]. Another large population-based study of 1151 patients who had undergone tumor nephrectomy reported that 10.5 % of this group had adverse renal outcomes over a 32-month follow-up (including ESKD, need for acute dialysis, rapidly progressive CKD, and stage 4 or worse CKD) [33]. In this study, radical nephrectomy had a hazard ratio of 1.75 (95 % confidence interval 1.02–2.99) for these adverse renal outcomes as compared to partial nephrectomy [33]. A study in the Medicare population of patients with T1a RCC demonstrated that patients who underwent radical nephrectomy had a higher rate of CKD than partial nephrectomy patients (20 vs. 11 %) and the 5-year freedom from new onset CKD was 82 % for those undergoing radical nephrectomy versus 91 % for those undergoing partial nephrectomy [34]. A dissenting study is that from the EORTC, where compared with radical nephrectomy, nephron sparing surgery substantially reduced the incidence of at least moderate renal dysfunction (eGFR < 60), although with available follow-up the incidence of advanced kidney disease (eGFR < 30) was relatively similar in the two treatment arms, and the incidence of kidney failure (eGFR < 15) was nearly identical [15] .
Given the known association of CKD with increased mortality, especially from cardiovascular disease it might be surmised that surgical approaches which achieve better long-term renal function while maintaining oncological cure rates would be associated with improved overall outcomes [35]. However, the data supporting better long-term outcomes with nephron sparing surgery over radical nephrectomy remain controversial and require further study. Many of the studies supporting improved outcomes with nephron-sparing surgery are single institution retrospective cohorts with selection bias and residual confounding. The only randomized trial, from the EORTC, did not find a survival advantage of partial versus radical nephrectomy [15]. However, a recent pooled analysis of 41,010 patients demonstrated that partial nephrectomy was associated with a 61 % risk reduction in developing CKD and 19 % risk reduction for all-cause mortality [36]. More research is needed to elucidate whether the anticipated consequences of preserving renal function translate into improved nonrenal, non-oncological outcomes .
Diagnosis of Subclinical CKD from the Tumor Nephrectomy Sample
The pathologic evaluation of tumor nephrectomy specimens has traditionally focused entirely on the renal mass with many parameters that must be analyzed and reported for every carcinoma, including size, Fuhrman grade, margin status, capsule or renal vein invasion, and other features . This focus has meant that the opportunity to diagnose noncancer kidney disease may be lost. In fact, approximately 60–88 % of such background diagnoses are not identified during the initial nephrectomy evaluation [29, 30]. A recent European survey of genitourinary pathologists revealed that over 25 % do not evaluate the nonneoplastic kidney parenchyma even though a portion of the tissue is properly sampled for every specimen [37]. In order to address these concerns, a modification of the College of American Pathologist kidney cancer protocol and checklist form was made to include reporting of nonneoplastic, contiguous disease [38]. Given that the majority of renal masses are stage 1 tumors with excellent outcomes, the status of the nonneoplastic kidney parenchyma is a critical pathologic parameter as it may discover previously unrecognized kidney pathology and aid postsurgical care . The further importance of finding renal parenchymal abnormalities is that those patients with these findings had a greater rise in serum creatinine levels postsurgery as compared to those with normal renal tissue (1.1 +/− 1.8 mg/dL vs. 0.2 +/− 0.2 mg/dL, p = 0.01) [39] . Other studies have also demonstrated that findings of renal parenchymal abnormalities in the nonneoplastic tissue were useful in predicting longer term kidney function [40, 41] .
Post-Nephrectomy Follow-up Care
Given the fact, that more patients are surviving with RCC and that CKD is common as the population ages, it follows that nephrologists will have an increasing role in the care of these patients . However, the nature of this role is unclear. As described above, CKD has been noted to be a common complication of nephrectomy for RCC. However, the move to nephron sparing surgery will hopefully diminish the likelihood of there being a large reduction in GFR following kidney cancer surgery and thus also lessen the burden of subsequent CKD. This may be offset by other factors such as the increasing prevalence of RCC as well as the older age of the population undergoing treatment for RCC. Furthermore, if pathologists consistently review nonneoplastic renal tissue, previously undiagnosed renal parenchymal diseases may be discovered which require nephrology evaluation and possibly therapy.
Thus, prudent recommendations for nephrology evaluation for the patient with RCC include the following: (1) the finding of any renal parenchymal pathological process on evaluation of noncancerous kidney tissue (such as previously undiagnosed glomerular or interstitial disease or significant (> 30 %) fibrosis) and (2) postoperative eGFR (once renal function is stable) < 60 ml/min. Furthermore, those patients with preoperative eGFRs < 60 ml/min would also benefit from nephrology consultation prior to surgery with close monitoring of postoperative kidney function .
In aggregate, data support a benefit of partial nephrectomy over radical nephrectomy for stage 1 renal carcinomas. Renal function is better preserved, oncological outcomes are not jeopardized, and overall mortality may be improved. Furthermore, data support having pathologists comment on the nonneoplastic renal tissue in the tumor nephrectomy specimen as these findings can help predict subsequent falls in GFR. There is an urgent need for communication between the nephrologist, urologist, and pathologist in deciding the right surgical and postoperative course of action for RCC .
Case #1 Follow-up and Discussion
The case described at the beginning of this chapter demonstrates the bidirectional nature of CKD–RCC interactions. This patient had shared risk factors for both diseases and in fact, had significant stage 3 CKD prior to nephrectomy that was not appreciated. Ten percent of tumor nephrectomy specimens demonstrate features of diabetic nephropathy; 2–9 % may have focal segmental glomerulosclerosis and another 20 % show hypertensive nephrosclerosis [29, 30]. His tumor nephrectomy specimen substantiated the findings of CKD along with features of hypertensive nephrosclerosis (correct answer to the question is c) and would predict a more rapid deterioration of kidney function postoperatively, which, in fact, was observed. More likely, a partial nephrectomy in this patient would have resulted in the oncologic cure but led to greater preservation of kidney function. This highlights the need for communication between the nephrologist, urologist, and pathologist in deciding the right surgical and postoperative course of action.
References
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US National Cancer Institute. Kidney cancer. http://www.cancer.gov/cancertopics/types/kidney. Accessed: 19. Aug. 2013.
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