End-Stage Kidney Disease Following Surgical Management of Kidney Cancer

Article

End-Stage Kidney Disease following Surgical Management of Kidney Cancer

Robert J. Ellis ,1,2,3,4 Daniel P. Edey,2,3 Sharon J. Del Vecchio,2,3,5 Megan McStea,3,6 Scott B. Campbell,1,6 Carmel M. Hawley,1,2,6,7 David W. Johnson ,1,2,6,7 Christudas Morais,2,3,5 Susan J. Jordan,4,8 Ross S. Francis,1,2,6,7 Simon T. Wood,2,3,5 Glenda C. Gobe,2,3,9,10 and Cancer Alliance Queensland

Abstract 1 Background and objectives We investigated the incidence of ESKD after surgical management of kidney cancer in Departments of Nephrology and the Australian state of Queensland, and described patterns in the initiation of kidney replacement therapy 5Urology, Princess resulting from kidney cancer across Australia. Alexandra Hospital, Brisbane, Australia; 2 Design, setting, participants, & measurements All newly diagnosed cases of kidney cancer in the Australian state of Centre for Kidney Disease Research, Queensland between January of 2009 and December of 2014 were ascertained through the Queensland Cancer Faculty of Medicine, Registry. There were 2739 patients included in our analysis. Patients who developed ESKD were identified using 6Australasian Kidney international classification of disease–10–coded hospital administrative data. Incidence rate and 3-year Trials Network, 8 cumulative incidence were calculated, and multivariable Cox proportional hazards models were used to identify Schools of Public Health and factors associated with ESKD. Additional descriptive analysis was undertaken of Australian population data. 9 Biomedical Sciences, and 10NHMRC Results The incidence rate of ESKD in all patients was 4.9 (95% confidence interval [95% CI], 3.9 to 6.2) per 1000 Chronic Kidney patient-years. The 3-year cumulative incidence was 1.7%, 1.9%, and 1.0% for all patients, and patients managed DiseaseCentrefor with radical or partial nephrectomy, respectively. Apart from preoperative kidney disease, exposures associated Research Excellence, $ University of with increased ESKD risk were age 65 years (adjusted hazard ratio [aHR], 2.0; 95% CI, 1.2 to 3.2), male sex (aHR, Queensland, 2.3; 95% CI, 1.3 to 4.3), preoperative diabetes (aHR, 1.8; 95% CI, 1.0 to 3.3), American Society of Anesthesiologists Brisbane, Australia; classification $3 (aHR, 4.0; 95% CI, 2.2 to 7.4), socioeconomic disadvantage (aHR, 1.6; 95% CI, 0.9 to 2.7), and 3Kidney Disease postoperative length of hospitalization $6 days (aHR, 2.1; 95% CI, 1.4 to 3.0). Australia-wide trends indicate that Research the rate of kidney replacement therapy after oncologic nephrectomy doubled between 1995 and 2015, from 0.3 to Collaborative, Translational Research 0.6 per 100,000 per year. Institute, Brisbane, Australia; 4Cancer Conclusions In Queensland between 2009 and 2014, one in 53 patients managed with radical nephrectomy and one Causes and Care in 100 patients managed with partial nephrectomy developed ESKD within 3 years of surgery. Group, QIMR – Berghofer Medical Clin J Am Soc Nephrol 13: 1641 1648, 2018. doi: https://doi.org/10.2215/CJN.06560518 Research Institute, Brisbane, Australia; and 7Australian and Introduction and 2015, 0.6% of patients who commenced kidney New Zealand Dialysis and Transplant In the developed world, the kidney is the sixth and replacement therapy (KRT) were recorded as having Registry, Adelaide, 13th most common site for primary malignancy in developed ESKD as a consequence of kidney cancer Australia men and women, respectively (1). Surgical manage- (6), which is similar to data from the USA, where ment with either radical (complete) or partial (nephron- kidney cancer patients constituted approximately Correspondence: sparing) nephrectomy is the mainstay of treatment. 0.5% of the KRT population from 1983 to 2007 (7). Mr. Robert J. Ellis, Removaloffunctionalkidneyparenchymacan Globally, the incidence of kidney cancer is rising, Translational Research ’ Institute (Level 5), increase a patient s risk of CKD (2). International particularly in Western countries (8), and in Australia 37 Kent Street, guidelines recommend partial nephrectomy when .3000 patients are diagnosed with kidney cancer Woolloongabba, QLD feasible, due to associations with better postoperative annually (9). Incidence rates have been steadily rising 4102, Australia. Email: kidney function and equivalent oncologic control since the 1980s, but mortality rates have remained [email protected] compared with radical nephrectomy (3,4). This has relatively static (9). It is unclear whether this is led to increased contemporary utilization of partial because patients are receiving more effective treat- nephrectomy (5). ment or whether a diagnosis is being made earlier in For patients who have limited life expectancy, the clinical course of disease; however, considering iatrogenic CKD is less likely to lead to a clinically trends of increasing incidental diagnosis of kidney significant event; however, for patients with a favor- cancer, the latter seems more likely (10,11). Regardless able prognosis, there is increased risk that CKD will of interpretation, these data demonstrate that the lead to a clinically significant end point, such as ESKD number of patients diagnosed with, and subsequently or cardiovascular events. In Australia between 2011 managed surgically for, kidney cancer is increasing www.cjasn.org Vol 13 November, 2018 Copyright © 2018 by the American Society of Nephrology 1641 1642 Clinical Journal of the American Society of Nephrology

and that, on average, patients diagnosed with kidney comorbidities, moderate-to-severe CKD and diabetes mel- cancer are expected to live longer. These two factors litus were included in the primary analysis. Sensitivity contribute to an increased lifetime risk of developing analyses were conducted that included additional comor- clinically significant iatrogenic CKD. bidities. Determination of comorbidities was limited to Previous population-based studies from the USA and hospitalizations within 12 preoperative months. American Canada have demonstrated that ESKD incidence after Society of Anesthesiologists (ASA) classification was re- surgical resection of kidney cancer is more common after corded at the time of surgery, and linked to cancer registry radical than partial nephrectomy, and in multimorbid/ data from hospital records, before being provided to elderly patients (12–15). The burden of ESKD after onco- investigators. ASA classification was grouped as 1–2and logical nephrectomy has not been previously evaluated in $3. Urban/rural place of residence and hospital location Australian populations. were assigned on the basis of the Accessibility/Remoteness The primary aim of this study was to characterize the Index of Australia (19). Patients were evaluated by area- burden of postoperative ESKD after radical and partial level socioeconomic status, grouped by tertiles (disadvan- nephrectomy, and to identify associations between patient taged, middle, advantaged) in accordance with the Aus- and health-service characteristics and this outcome, using a tralian Socioeconomic Indexes for Areas (Index of Relative large, population-based cohort of patients managed for Socioeconomic Disadvantage) (20). Patient-level socioeco- kidney cancer in the Australian state of Queensland. The nomic status and urban/rural status were determined from secondary aim was to evaluate long-term nationwide the postcode of the patient’s usual place of residence trends in kidney cancer-associated mortality and KRT recorded in the cancer registry, and provided in the data incidence. extract. Hospital volume was estimated by dividing the total number of surgical resections during the study period at each center by six, as per our previous publication (21). Materials and Methods Postoperative length of stay was calculated as the number Study Design and Population of days between the date of surgery and the date of All patients with any type of newly diagnosed kidney discharge. cancer across 43 hospitals in the Australian state of Queensland, diagnosed between January of 2009 and December of 2014, were ascertained through the Queens- Outcome land Cancer Registry, a state-wide registry that records all The primary outcome was ESKD. The date of ESKD was – newly diagnosed malignancies. Reporting cancer incidence assigned using ICD-10 coded hospital admissions data for to state-based registries is a legal requirement in Australia; any of: ESKD (N18.6), dependence on dialysis (Z99.2), or therefore, ascertainment of all cases is likely close to complete. kidney transplant (Z94.0). Patients undergoing a second There were 3799 patients identified. We excluded those who: radical nephrectomy were considered to have developed were aged ,18 years old (n=47), did not receive surgery ESKD on the date of their second procedure. (n=988), underwent concurrent bilateral nephrectomy (n=8), or had ESKD before surgery (n=17). The final sample in- Descriptive Analysis cluded 2739 patients. Patients younger than 18 years old were Additional data were obtained to descriptively evaluate excluded because it is likely that there are physiologic nationwide trends in kidney cancer–associated mortality differences in the response to nephrectomy between children and KRT. Incidence and mortality rates for kidney cancer in and adults (16). Patients who had ESKD before surgery were Australia were obtained from the Australian Institute of identified using international classification of disease–10 Health and Welfare (projected values used for 2016) (9,22), (ICD-10)–coded hospital administrative data. and KRT incidence data were provided by the Australia and New Zealand Dialysis and Transplant Registry (ANZ- Ethical Considerations DATA). Incidence and mortality rates were standardized Ethics approval was obtained from the University of to a population of 100,000 using the Australian 2001 Queensland Human Research Ethics Committee (Approval standard population, and trends were plotted over time. No. 2017001010). Access to patient information without consent was granted under the Queensland Public Health Statistical Analyses fi Act (Approval No. RD007218). All data were de-identi ed Patients were grouped by whether they developed ESKD before being provided to investigators. This study was by the date of data extraction; they were censored on the conducted in accordance with the Declaration of Helsinki. date of data extraction, or date of death. The 3-year cumulative incidence and incidence rate per 1000 person- Data Collection years were also calculated for all patients. Cumulative Data were extracted from the Queensland Cancer Reg- incidence was calculated over a 3-year period because this istry on the 14th of September 2017, and linked to electronic was the minimum follow-up time available for all patients. hospital admission and discharge data by the Queensland Time-to-event outcomes were assessed using multivariable Cancer Control and Analysis Team. Comorbidities before Cox proportional hazards regressions. Models were ad- and after surgery were determined from these administra- justed only for potential confounders, which were identi- tive data using a validated algorithm that incorporates fied using directed acyclic graphs. The proportional ICD-10 codes (17). The output is a list of comorbidities for hazards assumption was checked through formal hypoth- each patient, which are determined using the same thresh- esis testing of Schoenfeld residuals, and visual tests of the olds as the Charlson comorbidity index (18). From these interaction between groups and survival times. A sensitivity Clin J Am Soc Nephrol 13: 1641–1648, November, 2018 ESKD after Surgery for Kidney Cancer, Ellis et al. 1643

analysis was undertaken that excluded all patients who underwent more than one nephrectomy during the study Table 1. Characteristics of 2739 patients managed surgically period. As an additional sensitivity analysis, models were for kidney cancer assessed using a competing risk regression, considering all- Postoperative ESKDa cause mortality as a competing risk, using the method of Fine Characteristics and Gray (23). When adjusting for health-service character- No Yes istics, clustering by hospital code was accounted for using (n=2671) (n=68) robust sandwich estimators. Analysis was performed using Patient characteristics Stata 14.0 (StataCorp, College Station, TX) and two-sided a Age at diagnosis, yr – – was set at 0.05. Median (IQR) 62 (53 70) 66 (61 74) ,65 1606 (60) 30 (44) $65 1065 (40) 38 (56) Sex Results Female 933 (35) 13 (19) Incidence of ESKD Male 1738 (65) 55 (81) Of 2739 patients, 68 developed ESKD by the end of the Preoperative kidney disease No 2637 (99) 53 (78) follow-up period. Patient characteristics are outlined in Yes 34 (1) 15 (22) Table 1, and ESKD by most-likely precipitating cause is Preoperative diabetes mellitus presented in Figure 1. The median (interquartile range) No 2354 (88) 54 (79) follow-up time was 59.4 (42.9–79.2) months. The median Yes 317 (12) 14 (21) ASA classification time from the date of surgery until the development of 1–2 1419 (53) 15 (22) ESKD was 27.9 (11.8–43.4) months. The incidence rate of $3 883 (33) 42 (62) Missing 369 (14) 11 (16) ESKD in all patients, and patients managed with radical b fi Socioeconomic status and partial nephrectomy, was 4.9 (95% con dence interval Disadvantaged 606 (23) 22 (32) [95% CI], 3.9 to 6.2), 5.2 (95% CI, 4.0 to 6.8), and 3.7 (95% CI, Middle 1696 (63) 39 (57) 2.1 to 6.5) cases per 1000 person-years. The 3-year cumu- Advantaged 369 (14) 7 (10) c lative incidence of ESKD was 1.7% (1 in 59), 1.9% (1 in 53), Place of residence Major city 1618 (61) 41 (60) and 1.0% (1 in 100) for all patients, and patients managed Inner regional 648 (24) 17 (25) with radical and partial nephrectomy, respectively. A Rural 404 (15) 10 (15) d Kaplan–Meier graph comparing survival estimates for Health-service characteristics Nephrectomy type radical and partial nephrectomy is presented in Figure 2, Partial 625 (23) 12 (18) and a cumulative incidence function curve is presented in Radical 2046 (77) 56 (82) Supplemental Figure 1. Surgical approach Open 807 (30) 24 (35) Laparoscopic 1864 (70) 44 (65) Associations with ESKD Multiple surgeriese Of the patient characteristics evaluated in this study, No 2614 (98) 59 (87) age$65 years compared with younger patients (adjusted Yes 57 (2) 9 (13) Hospital type hazard ratio [aHR], 2.0; 95% CI, 1.2 to 3.2), male sex (aHR, Private 1239 (46) 29 (43) 2.3; 95% CI, 1.3 to 4.3), preoperative kidney disease (aHR, Public 1432 (54) 29 (57) f 15.0; 95% CI, 8.3 to 27.0), preoperative diabetes mellitus Hospital location $ Major city 2162 (81) 53 (78) (aHR, 1.8; 95% CI, 1.0 to 3.3), and an ASA score 3(aHR, Inner regional 353 (13) 11 (16) 4.0; 95% CI, 2.2 to 7.4) were significantly associated with Outer regional 156 (6) 4 (6) ESKD (Table 2). Patients in the lowest tertile of socioeco- Hospital volume, resections/yrf – – nomic status (disadvantaged) were also at increased risk of Median (IQR) 25 (14 56) 25 (14 41) ,20 963 (36) 26 (38) ESKD, although this association did not reach conventional $20 1708 (64) 42 (62) levels of statistical significance (aHR, 1.6; 95% CI, 0.9 to 2.7). Postoperative length of stay The only health-service characteristic related to ESKD was Median (IQR) 4(3–6) 6 (4–9) – length of postoperative stay $6 days, compared with 1–5 1 5d 1891 34 $6d 780 34 days (aHR, 2.1; 95% CI, 1.4 to 3.0). There were no differences when analyses were performed with a competing risk re- Data presented as: count (%) or median (interquartile range). IQR, gression, considering death as a competing event (Supple- interquartile range; ASA, American Society of Anesthesiologists. mental Table 1). No differences were observed when patients aESKD defined as admission for hemodialysis, kidney who underwent more than one nephrectomy were excluded transplant, ESKD, or a second radical nephrectomy. bSocioeconomic indexes for areas index of relative socioeco- (Supplemental Table 2). Refer to Supplemental Tables 3 and 4 nomic advantage and disadvantage (tertiles). for sensitivity analyses evaluating additional comorbidities. cAccessibility/remoteness index of Australia; rural encom- passes outer regional and remote categories. dSurgery characteristics are for the first procedure only. Nationwide Trends e Includes patients who had more than one procedure, in any The age-standardized incidence rate of kidney cancer in combination of radical or partial nephrectomy. Of the nine Australia has been increasing since 1982, whereas deaths patients who developed ESKD, seven of these underwent two attributable to kidney cancer have remained fairly static radical nephrectomies at different time points. f (Figure 3A). Incidence of KRT due to kidney cancer in Number of surgeries for kidney cancer at each center/yr. Australia has been steadily increasing since the first recorded case of this in 1974 (Figure 3B). Similarly, the 1644 Clinical Journal of the American Society of Nephrology

Figure 2. | Kaplan-Meier survival estimates curve showing ESKD occurred more frequently following radical nephrectomy, although Figure 1. | The predisposing factor for ESKD was uncertain for most estimates did not reach conventional levels of statistical significance. patients. Of the 68 patients who developed ESKD after surgical Graph comparing freedom from ESKD for patients managed with management of kidney cancer, 15 of these patients had preoperative radical (broken line) compared with partial (solid line) nephrectomy. moderate-to-severe CKD, seven patients went on to have a second Differences in the incidence of ESKD between the two procedures did nephrectomy for cancer management, and for 46 patients the cause is not reach conventional levels of statistical significance (P=0.26). uncertain. Of these 46 patients, 28 had an ASA score $3 (black), 11 had an ASA score ,3 (dark gray), and ASA score was not known for the remaining seven patients (light gray). There were eight patients in this 1.3; 95% CI, 0.8 to 2.0), which was also the case in this dataset who were excluded because they received a bilateral radical study. This is most likely an issue of inadequate power due nephrectomy (these patients are included in this figure because they also developed ESKD). to the low event count. It is also possible that the incidence of ESKD after partial nephrectomy was biased due to unmeasured confounding by indication, where patients average proportion of annual incident KRT cases that are undergoing partial nephrectomy with an absolute indica- attributable to kidney cancer has risen from 0.2% in the tion (e.g., patients with a single functional kidney, preex- 1970s to 0.6% in 2015 (Figure 3C). When assessing cancer- isting severe CKD, or bilateral tumors) were at higher risk specific deaths as a ratio of incident kidney cancer cases, of ESKD than those undergoing elective partial nephrec- there is a marked negative trend over time; whereas, when tomy (26). considering KRT due to kidney cancer as a ratio of incident In an analysis similar to this study conducted in Ontario, kidney cancer cases, this ratio steadily rises over time Canada, Yap et al. (13) found that, in a cohort of 7153 (Figure 3D). patients managed for kidney cancer between 2003 and 2010, partial nephrectomy was associated with a significantly lower risk of ESKD compared with radical nephrec- Discussion tomy (aHR, 0.4; 95% CI, 0.3 to 0.8). This supports our The aim of this study was to characterize the burden of inference that failure to discern a difference between the ESKD in patients managed surgically for kidney cancer. two procedures in this study was a consequence of in- Most significantly, we found that 1.7% of patients managed adequate power. A recent systematic review of 21 studies surgically for kidney cancer (1.9% and 1.0% of those comparing radical and partial nephrectomy (total managed with radical and partial nephrectomy, respec- n=11,204) also suggest benefits in terms of kidney function tively) developed ESKD within 3 years of surgery (i.e.,1in after partial nephrectomy (27). Mir et al. (27) demonstrated 53 patients managed with radical nephrectomy, and 1 in that patients managed with partial nephrectomy had a 100 patients managed with partial nephrectomy). significantly lower risk of developing CKD (eGFR,60 The incidence rates reported in this study were reason- ml/min per 1.73 m2) postoperatively compared with those ably similar to the only other report of ESKD incidence after managed with radical nephrectomy (relative risk, 0.36; nephrectomy conducted in the Asian-Pacific region. A P,0.001). recent population-based study of 3636 Taiwanese nephrec- In clinical practice, it is assumed that only patients with tomy patients conducted by Lin et al. (24) reported ESKD clearly perturbed preoperative kidney function or anat- incidence rates of 6.9 and 5.5 cases per 1000 person-years in omy are at significant risk of ESKD after nephrectomy (3). patients managed with radical and partial nephrectomy. We were able to establish that potential risk factors for Our corresponding point-estimates were 5.2 and 3.7 cases incident ESKD were older age, the presence of diabetes per 1000 person-years; although these were slightly lower, mellitus, and socioeconomic disadvantage, which are this is most likely explained by the fact that Taiwan has the well known risk factors for CKD in the Australian world’s highest incidence of ESKD (25), indicating that population (28); and high ASA classification and male Taiwanese kidney cancer patients may generally be at sex, both of which are associated with CKD after ne- higher risk of ESKD than Australian kidney cancer patients. phrectomy (29,30). Lin et al. did not find a statistically significant difference in With these possible risk factors in mind, preoperative the incidence of ESKD between the two procedures (IRR, and ongoing screening for at-risk nephrectomy patients Clin J Am Soc Nephrol 13: 1641–1648, November, 2018 ESKD after Surgery for Kidney Cancer, Ellis et al. 1645

Table 2. Risk factors for developing ESKD after surgical management of kidney cancer (n=2739)

Crude Adjusted Characteristics Person-Years Number of Events Rate HR (95% CI) HR (95% CI) Patient characteristics Age at diagnosis, yr ,65 8543 30 3.5 1 1 $65 5342 38 7.1 2.0 (1.2 to 3.2) 2.0 (1.2 to 3.2) Per 5 yr ———1.2 (1.1 to 1.3) 1.2 (1.1 to 1.3) P value 0.005 0.005 Sex Female 4990 13 2.6 1 1 Male 8894 55 6.2 2.3 (1.3 to 4.2) 2.3 (1.3 to 4.3) P value 0.006 0.006 Preoperative kidney diseasea No 13,670 53 3.9 1 1 Yes 214 15 70.0 17.0 (9.9 to 31.0) 15.0 (8.3 to 27.0) P value ,0.001 ,0.001 Preoperative diabetes mellitusb No 12,350 54 4.4 1 1 Yes 1535 14 9.1 2.0 (1.1 to 3.6) 1.8 (1.0 to 3.3) P value 0.02 0.05 ASA classiﬁcationb,c 1–2 7650 15 2.0 1 1 $3 4396 42 9.6 4.7 (2.6 to 8.5) 4.0 (2.2 to 7.4) P value ,0.001 ,0.001 Socioeconomic status Middle/advantaged 10,724 46 4.3 1 1 Disadvantaged 3160 22 7.0 1.6 (0.9 to 2.7) 1.6 (0.9 to 2.7) P value 0.06 0.06 Place of residence Major city 8412 41 4.9 1 1 Inner regional 3392 17 5.0 1.0 (0.6 to 1.8) 1.0 (0.6 to 1.8) Rural 2080 10 4.8 1.0 (0.5 to 2.0) 1.0 (0.5 to 2.0) P value 0.90 0.99 Health-service characteristics Nephrectomy typed Partial 3238 12 3.7 1 1 Radical 10,657 56 5.3 1.4 (0.9 to 2.2) 1.3 (0.8 to 2.0) P value 0.08 0.26 Surgical approache Open 4148 24 5.8 1 1 Laparoscopic 9736 44 4.5 0.8 (0.5 to 1.3) 0.7 (0.4 to 1.4) P value 0.32 0.37 Hospital typef Private 6508 29 4.5 1 1 Public 7378 39 5.3 1.2 (0.8 to 1.7) 1.3 (0.9 to 1.9) P value 0.38 0.13 Hospital location Major city 11,265 53 4.7 1 1 Inner regional 1849 11 5.9 1.3 (0.7 to 2.1) 1.2 (0.7 to 2.0) Outer regional 771 4 5.2 1.1 (0.7 to 1.7) 1.0 (0.6 to 1.6) P value 0.67 0.86 Hospital volume, resections/yrg ,20 4909 26 5.3 1 1 $20 8974 42 4.7 0.9 (0.6 to 1.4) 1.0 (0.6 to 1.6) P value 0.59 0.93 Postoperative length of stayh 1–5d 9866 34 3.4 1 1 $6d 4018 34 8.6 2.5 (1.6 to 4.0) 2.1 (1.4 to 3.0) Per day ———1.07 (1.03 to 1.10) 1.04 (1.01 to 1.07) P value ,0.001 0.002

Hazard ratio (HR)and 95% conﬁdence interval (95% CI) estimated using Cox proportional hazards model. Reported rate is per 1000 patient-yr. All adjusted estimates were adjusted for age and sex; additional adjustment variables are included as footnotes. For all health-service characteristics, clustering by hospital code was accounted for using robust sandwich estimators. —,notapplicable;ASA,AmericanSocietyofAnesthesiologists. aAdditionally adjusted for diabetes mellitus and place of residence. bAdditionally adjusted place of residence. cThere were missing data for 369 observations. dAdditionally adjusted for hospital location and hospital volume. eAdditionally adjusted for nephrectomy type, hospital location, and hospital volume. fAdditionally adjusted for socioeconomic status. gAdditionally adjusted for hospital location. hAdditionally adjusted for preoperative diabetes and kidney disease, ASA classiﬁcation, nephrectomy type, and surgical approach. 1646 Clinical Journal of the American Society of Nephrology

Figure 3. | Australia-wide trends in the incidence of kidney replacement therapy, and incidence and mortality of kidney cancer show that mortality rates for kidney cancer are dropping, but incident kidney replacement therapy (KRT) following the management of kidney cancer is increasing. (A) Age-adjusted incidence (blue) and mortality (red) rates per 100,000 population for kidney cancer in Australia. (B) Age-adjusted incidence rate of KRTattributable to kidney cancer in Australia per 100,000 population. (C) Number of incident KRT cases in Australia (black) compared with the percentage of these cases attributable to kidney cancer (green). (D) The number of deaths as a ratio of incident kidney cancer cases (red) and the number of incident KRT cases due to kidney cancer as a ratio of incident kidney cancer cases (green). Data from the Australian Institute of Health and Welfare, and the Australia and New Zealand Dialysis and Transplant Registry.

may improve patient outcomes, allowing for earlier ap- Before this study, the only population-level data on propriate referral to a nephrologist, with subsequent ESKD after surgical management of kidney cancers in implementation of a multidisciplinary approach to ongoing Australia were reported by the ANZDATA registry. Com- management decisions (28,31). Foreseeable benefits of early pared with Queensland kidney cancer patients in this study involvement of a nephrologist could include slower disease who developed ESKD, the proportion of patients recorded progression, reductions in mortality and hospitalization by ANZDATA to have developed ESKD as a consequence rates, improvements in vascular access outcomes, and a of kidney cancer is considerably smaller. ANZDATA higher likelihood of transplantation, all of which have been presumably underestimates the true incidence of ESKD observed in the general population (32–35). after surgical management of kidney cancers because it Another finding of interest was that a longer post- only reports patients who received KRT. It is not imme- operative stay was associated with ESKD. Patients diately clear how many patients who develop ESKD after with a greater number of comorbidities, older patients, nephrectomy do not begin KRT. As only one cause of patients who experience perioperative surgical compli- kidney disease can be recorded, this may also affect the cations, and patients undergoing more extensive/in- incidence reported in this registry, because the cause of vasive surgery are more likely to have a longer period of ESKD recorded in the registry is that which the nephrol- postoperative hospitalization (36). Although these var- ogists considered to be the most important. The most iables were adjusted for (with the exception of peri- salient observations from these nationwide data were that operative complications), residual confounding may both kidney cancer incidence and the incidence of KRT as a have played a role. We have previously observed that consequence of kidney cancer are rising; whereas, the patients from our center who have a low eGFR before number of kidney cancer-associated deaths has remained nephrectomy tend to have a longer postoperative length stable. One explanation is that more patients are being of stay (37), which may also partially explain the present diagnosed with incidental kidney masses and undergoing finding. surgical management, hence potentially reducing the Clin J Am Soc Nephrol 13: 1641–1648, November, 2018 ESKD after Surgery for Kidney Cancer, Ellis et al. 1647

mortality rate due to overdiagnosis bias (38), while driving and socioeconomic disadvantage were all associated with up the rate of KRT due to more frequent surgical man- the development of ESKD. Nationwide data indicated that agement. KRT commencement after surgical management for kidney Another possible explanation is that the likelihood of cancers increased proportionally to the number of patients KRT being offered to patients developing ESKD subse- diagnosed with kidney cancer, whereas the ratio of deaths quent to nephrectomy has increased over time, due to to incident kidney cancer cases decreased. This study has systemic changes in the provision of KRT in Australian highlighted that patients undergoing nephrectomy are hospitals. Between the years of 1991 and 1998, there was no subjected to potential harms, which need to be carefully difference in the KRT commencement rate for patients aged balanced against benefits of surgery. #64 years old; however, for the age groups 65–74 and 75– 84 years old, there was an increase of approximately 200 Acknowledgments and 100 patients per million population, respectively, over R.J.E. was supported by an Australian Government Research this period (39). Considering that the average age of kidney Training Stipend during the conduct of this study. D.W.J. is a current cancer diagnosis is approximately 60 years old (40), and recipient of a National Health and Medical Research Council $ patients aged 65 years old were more likely to develop Practitioner Fellowship. ESKD after nephrectomy compared with younger patients Data used in the preparation of this article were obtained from (Table 1), greater tendency to offer dialysis to older patients Queensland Cancer Registry managed by the Queensland Cancer over time could also partially explain the trends seen in Control and Analysis Team, under the auspices of the Queensland Figure 3. Notwithstanding, the observed trend most likely Cancer Control Safety and Quality Partnership, a gazetted quality fl re ects, at least in part, a greater number of kidney cancer assurance committee under Part 6, Division 1 of the Hospital and cases being diagnosed and managed surgically over time. Health Boards Act 2011 (Gazetted December 10, 2004). Cancer Al- The strengths of this study were its large size, population- liance Queensland contributed data but did not participate in the based sampling strategy, and minimum follow-up time analysis or writing of this manuscript. Some population-level data of 3 years, which allowed for a comprehensive and were supplied by the Australia and New Zealand Dialysis and complete evaluation of the incidence of ESKD after ne- Transplant Registry (ANZDATA). The interpretation and reporting phrectomy in Queensland, Australia. Limitations included of these data are the responsibility of the authors and in no way the fact that there were minimal patient-level data avail- should be seen as an official policy or interpretation of ANZDATA. able, which hindered our ability to investigate causes of The authors also acknowledge the Australian Institute of Health and fi ESKD in signi cant detail. In particular, individual mea- Welfare as an additional source of population-level data used in this sures of kidney function and albuminuria were unavail- study. able, which may have provided greater insight into populations at higher risk of ESKD. 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