Advertisement

Below Safety Limits, Every Unit of Glomerular Filtration Rate Counts: Assessing the Relationship Between Renal Function and Cancer-specific Mortality in Renal Cell Carcinoma

      Abstract

      Background

      The hypothesis that renal function could influence oncological outcomes is supported by anecdotal literature.

      Objective

      To determine whether estimated glomerular filtration rate (eGFR) is related to cancer-specific mortality (CSM) in patients who had undergone surgery for renal cell carcinoma (RCC).

      Design, setting, and participants

      A retrospective analysis of 3457 patients who underwent radical (39%) or partial nephrectomy (61%) for cT1–2 RCC between 1990 and 2015.

      Outcome measurements and statistical analysis

      The eGFR was calculated by the Chronic Kidney Disease Epidemiology Collaboration equation. CSM was analyzed in a multivariable competing-risk framework, estimating the subdistribution hazard ratio (SHR) accounting for deaths from other causes. The relationship between eGFR and CSM was investigated from multiple statistical approaches—extended Cox regression with eGFR incorporated as a time-dependent covariate, landmark analysis, and joint modeling. Other predictors were selected by competing-risk random forest method and backward elimination.

      Results and limitations

      The relationship between eGFR and CSM was graphically described by a linear spline, i.e. a continuous piecewise linear function with two lines joined by a knot. For eGFR treated as a time-dependent covariate, the knot was located at 65 ml/min; at landmark analysis with eGFR at the baseline, 12 mo, and last functional follow-up, the knots were 85, 60, and 65 ml/min, respectively. In multivariable competing-risk analysis, CSM was associated with eGFR only for values of eGFR below these cutoffs, with SHRs for every 10 ml/min of reduction in eGFR of 1.25 (p = 0.003), 1.16 (p = 0.028), 1.44 (p = 0.02), and 1.16 (p = 0.042), corresponding to time-dependent eGFR, and eGFR at baseline, 12 mo, and last functional follow-up, respectively. Joint modeling confirmed these results. A retrospective design with inherent biases in data collection represents a limitation.

      Conclusions

      In patients undergoing surgery for RCC, renal function should be preserved in order to improve cancer-related survival.

      Patient summary

      The relationship between renal function and probability of dying due to renal cancer is complex. The present study found a correlation between glomerular filtration rate and cancer specific mortality that could reconsider the oncological role of renal function in patients undergoing surgery for renal cancer.

      Keywords

      To read this article in full you will need to make a payment

      Subscribe:

      Subscribe to European Urology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Ljungberg B.
        • Bensalah K.
        • Canfield S.
        • et al.
        EAU guidelines on renal cell carcinoma: 2014 update.
        Eur Urol. 2015; 67: 913-924
        • Campbell S.C.
        • Novick A.C.
        • Belldegrun A.
        • et al.
        Guideline for management of the clinical T1 renal mass.
        J Urol. 2009; 182: 1271-1279
        • Kim S.P.
        • Thompson R.H.
        • Boorjian S.A.
        • et al.
        Comparative effectiveness for survival and renal function of partial and radical nephrectomy for localized renal tumors: a systematic review and meta-analysis.
        J Urol. 2012; 188: 51-57
        • Wu J.
        • Suk-Ouichai C.
        • Dong W.
        • et al.
        Analysis of survival for patients with chronic kidney disease primarily related to renal cancer surgery.
        BJU Int. 2018; 121: 93-100
        • Sun M.
        • Trinh Q.D.
        • Bianchi M.
        • et al.
        A non-cancer-related survival benefit is associated with partial nephrectomy.
        Eur Urol. 2012; 61: 725-731
        • Larcher A.
        • Capitanio U.
        • Terrone C.
        • et al.
        Elective nephron sparing surgery decreases other cause mortality relative to radical nephrectomy only in specific subgroups of patients with renal cell carcinoma.
        J Urol. 2016; 196: 1008-1013
        • Van Poppel H.
        • Joniau S.
        • Albersen M.
        Nephron sparing for renal cell carcinoma: whenever possible?.
        Eur Urol Focus. 2016; 2: 656-659
        • Christensson A.
        • Savage C.
        • Sjoberg D.D.
        • et al.
        Association of cancer with moderately impaired renal function at baseline in a large, representative, population-based cohort followed for up to 30 years.
        Int J Cancer. 2013; 133: 1452-1458
        • Lowrance W.T.
        • Ordoñez J.
        • Udaltsova N.
        • Russo P.
        • Go A.S.
        CKD and the risk of incident cancer.
        J Am Soc Nephrol. 2014; 25: 2327-2334
        • Weng P.H.
        • Hung K.Y.
        • Huang H.L.
        • Chen J.H.
        • Sung P.K.
        • Huang K.C.
        Cancer-specific mortality in chronic kidney disease: longitudinal follow-up of a large cohort.
        Clin J Am Soc Nephrol. 2011; 6: 1121-1128
        • Vajdic C.M.
        • McDonald S.P.
        • McCredie M.R.
        • et al.
        Cancer incidence before and after kidney transplantation.
        JAMA. 2006; 296: 2823-2831
        • Shebl F.M.
        • Warren J.L.
        • Eggers P.W.
        • Engels E.A.
        Cancer risk among elderly persons with end-stage renal disease: a population-based case-control study.
        BMC Nephrol. 2012; 13: 65
        • Levey A.S.
        • Stevens L.A.
        Estimating GFR using the CKD Epidemiology Collaboration (CKD-EPI) creatinine equation: more accurate GFR estimates, lower CKD prevalence estimates, and better risk predictions.
        Am J Kidney Dis. 2010; 55: 622-627
        • Pintilie M.
        Competing risks. A practical perspective.
        John Wiley & Sons Ltd, Chichester, England2006
        • Beyersmann J.
        • Schumacher M.
        Time-dependent covariates in the proportional subdistribution hazards model for competing risks.
        Biostatistics. 2008; 9: 765-776
        • Putter H.
        Handbook of survival analysis.
        Chapman & Hall/CRC, Boca Raton, FL2013: 441-456 (Chapter 21)
        • Ishwaran H.
        • Kogalur U.B.
        • Blackstone E.H.
        • Lauer M.S.
        Random survival forests.
        Ann Appl Stat. 2008; 2: 841-860
        • Spiriti S.
        • Eubank R.
        • Smith P.
        • Young D.
        Knot selection for least-squares and penalized splines.
        J Stat Comput Simul. 2013; 83: 1020-1036
        • Muggeo V.M.R.
        Estimating regression models with unknown break-points.
        Stat Med. 2003; 22: 3055-3071
        • Elashoff R.
        • Li G.
        • Li N.
        Joint modeling of longitudinal and time-to-event data.
        Chapman and Hall/CRC, Boca Raton, FL2016
        • Chronic Kidney Disease Prognosis Consortium
        • Matsushita K.
        • van der Velde M.
        • et al.
        Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis.
        Lancet. 2010; 375: 2073-2081
        • Kaushik D.
        • Kim S.P.
        • Childs M.A.
        • et al.
        Overall survival and development of stage IV chronic kidney disease in patients undergoing partial and radical nephrectomy for benign renal tumors.
        Eur Urol. 2013; 64: 600-606
        • Mok Y.
        • Matsushita K.
        • Sang Y.
        • et al.
        Association of kidney disease measures with cause-specific mortality: the Korean Heart Study.
        PLoS One. 2016; 11: e0153429
        • Iff S.
        • Craig J.C.
        • Turner R.
        • et al.
        Reduced estimated GFR and cancer mortality.
        Am J Kidney Dis. 2014; 63: 23-30
        • Kim Y.W.
        • Kim W.T.
        • Yun S.J.
        • et al.
        Preoperative chronic kidney disease status is an independent prognostic factor in patients with renal cell carcinoma.
        Ann Surg Oncol. 2015; 22: 4098-4103
        • Van Poppel H.
        • Da Pozzo L.
        • Albrecht W.
        • et al.
        A prospective, randomized EORTC intergroup phase 3 study comparing the oncologic outcome of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma.
        Eur Urol. 2011; 59: 543-552
        • Scosyrev E.
        • Messing E.M.
        • Sylvester R.
        • Campbell S.
        • Van Poppel H.
        Renal function after nephron-sparing surgery versus radical nephrectomy: results from EORTC randomized trial 30904.
        Eur Urol. 2014; 65: 372-377
        • Thompson R.H.
        Partial versus radical nephrectomy: the debate regarding renal function ends while the survival controversy continues.
        Eur Urol. 2014; 65: 378-379
        • Kato S.
        • Chmielewski M.
        • Honda H.
        • et al.
        Aspects of immune dysfunction in end-stage renal disease.
        Clin J Am Soc Nephrol. 2008; 3: 1526-1533
        • Betjes M.G.
        • Litjens N.H.
        Chronic kidney disease and premature ageing of the adaptive immune response.
        Curr Urol Rep. 2015; 16: 471
        • Antonelli A.
        • Furlan M.
        • Sodano M.
        • et al.
        Features, risk factors and clinical outcome of “very late” recurrences after surgery for localized renal carcinoma: a retrospective evaluation of a cohort with a minimum of 10 years of follow up.
        Int J Urol. 2016; 23: 36-40