Assessment and implications of chronic kidney disease (CKD)

Kidney cancer. Principles and practice. Second edition. Primo N. Lara, Jr. Eric Jonasch (Editors). Springer International Publishing (2015)


The systematic review by the RCC guidelines committee of the AUA highlights the priority of goals when managing localized RCC: (1) optimize cancer treatment, (2) preserve renal function, and if the first two goals are met, (3) utilize a minimally invasive technique while minimizing the risk of adverse postoperative events [5]. Published series have established the oncologic efficacy of nephron-sparing surgery (NSS) for pT1a and pT1b renal tumors [5, 39–42]. Despite these findings and other data indicating that PN confers a non-oncological survival advantage, nationally the use of PN for tumors less than 4 cm continues to be less than 30% [43]. As more incidental renal masses continue to be detected and the adverse relationship between long-term CKD and morbidity/mortality is uncovered, the importance of renal functional preservation continues to be paramount.

Traditionally, serum creatinine (sCr) has been used to measure the presence or absence of renal dysfunction; however, this can be a misleading value, since sCr can be affected by age, gender, muscle mass, and diet. Furthermore, since creatinine is both secreted and reabsorbed by renal tubules, certain medications, such as cimetidine and sulfonamides, can alter sCr by inhibiting its tubular secretion. Recent data suggest that serum creatinine measurements are a poor tool to estimate the degree of renal impairment [9, 10]. In fact, in a recent cross-sectional analysis comparing the National Health and Nutrition Examination Surveys (NHANES) between 1988–1994 and 1999–2004 consisting of approximately 29,000 patients, 25% of patients with a “normal” sCr had chronic kidney disease (CKD) stage 3 or greater, as defined by the National Kidney Foundation [44]. With the recent data underscoring the prevalence of CKD in the general population, attention has focused on estimating the glomerular filtration rate (GFR) as a measure of a patient’s renal function. More precise measures of GFR have recently been adopted including the MDRD and CKDEPI. Therefore, the socioeconomic and health implications of significant national underutilization of NSS are likely clinically underestimated.

The risk of postoperative chronic kidney disease after RN when compared to PN has been well studied. McKiernan et al. showed that the risk of having a postoperative baseline sCr greater than 2.0 mg/dL was significantly greater following RN when compared to a PN [45]. A more precise quantification of CKD after nephrectomy was undertaken by Huang et al. Using the MDRD equation to estimate GFR, the authors found in a multivariable analysis that RN was an independent risk factor for patients developing an eGFR of less than 60 ml/min and less than 45 ml/min [46]. The incidence of baseline renal dysfunction (eGFR <60) in their study was 26%.

The relationship between CKD and the risks of death, cardiovascular events, and hospitalization rates is clinically relevant but has previously not received much attention because it is often an event that occurs well past the initial surgical loss of nephrons. With each 15 ml/min diminution of eGFR below 60 ml/min, the risk of death, cardiovascular events, and hospitalization increases [47]. For example, the adjusted hazard ratio for death in a patient with an eGFR of 45–59 ml/min is 1.2 while it is 5.9 for an eGFR less than 15 ml/ min [47]. Furthermore, the interaction between age and CKD and their effects on survival requires the urologist to diligently assess an elderly patient’s renal function preoperatively. In one study, more than 50% of patients older than 75 years died within 2 years after starting dialysis [48]. The median survival time for this aged population on dialysis was 22 months.

The prevalence of CKD stage III or higher based on NHANES 1999–2004 data has increased to over 8% [44]. It is unclear if a population enriched for patients with radiographically concerning RCC reflects this trend or has a potentially higher risk of CKD. In a recent review of our institutional kidney cancer database, we showed that although 88% of all patients presenting for surgery with a solid renal mass at our institution had a “normal” sCr (=1.4 mg/dl), 12.5% of these patients had CKD stage III when estimating GFR [11]. Moreover, 23% of patients 70 years old or greater with a seemingly normal sCr had CKD stage III. These findings support reports by other authors who have argued for more precise measurement of a patient’s renal function, either by the MDRD equation or the newly developed Chronic Kidney Disease-Epidemiology Study equation, to better assess a patient’s renal function [9, 10]. Finally, the national average of NSS, ranging from 27% [49] to 40% [43] for pT1a tumors, is concerning in light of our findings showing an underestimation of chronic kidney disease by routine serum creatinine monitoring. This study highlights the fact that both eGFR and CKD stage must be routinely calculated and clinical decisions based on these variables not sCr, especially in the elderly.

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