Chronic Kidney disease in CAT patients

During the ICTHIC webinar, “What is the profile of the real-world CAT patient?” Dr. Corinne Isnard Bagnis gave a lecture about chronic kidney disease in CAT patients. Here, we summarize the key messages of her speech. You can also watch Corinne I. Bagnis’s lecture in the video below and the full webinar recording here.

Chronic kidney disease and cancer

Chronic kidney disease (CKD) is a global health burden associated with age-related renal function decline. All stages of CKD are associated with increased risks of cardiovascular morbidity, premature mortality, and/or decreased quality of life. CKD has a high global prevalence estimated at around 10.6% at stages 3 to 5 [1].

Some studies tried to define the population living with CKD and cancer.

In France and Belgium, 12 to 16% of patients with cancer exhibit an estimated glomerular filtration rate (GFR) below 60 ml/min/1.73 m² (stage 3 CKD or higher) [2-4]. In the US, this rate is higher, up to 22% [5]. Also, in patients with cancer aged 65 years or older, the prevalence of renal failure is higher, with 65% having a GFR below 90 ml/min/1.73 m² (stage 2 CKD) and 20% below 60 [6].

In patients with cancer, the GFR value impacts survival: a significant difference exists between survival if the patient has a normal renal function or CKD stage 3, 4, or 5.

A study highlighted that CKD in patients with cancer was associated with an increased risk of death, with an adjusted hazard ratio of 1.12 for patients with a GFR of 30-59 ml/min/1.73 m² and 1.75 for patients with a GFR lower than 30 ml/min/1.73 m² [7].

A study tried to analyze the reasons behind this increased mortality risk, investigating the determinants and the mortality associated with the use of drugs that are contraindicated or require dose adjustment according to kidney function [8].

The overall percentage of exposure to the risk of inappropriate drug use was 52.5% in those with a GFR below 60 ml/min/1.73 m² and 96% in those below 30 mL/min/1.73 m². The use of contraindicated drugs was uncommon among community-dwelling older people, but drug use requiring dose adjustment may concern more than 10% [8].

Results showed that using drugs requiring dose adjustment is associated with excess mortality among community-dwelling elderly with impaired kidney function, regardless of age, gender, and several potential confounders [8].

What is the impact of CKD on drug handling and thrombosis risk?

In CKD patients, generally, only the drugs that undergo renal elimination are a source of concern. However, many experimental and clinical studies showed that uremia and CKD could impact all the stages of the drug’s pharmacokinetic trajectory [9, 10]. For example, in patients with severe CKD (stages 4 or 5 or in dialysis), gastric pH changes with a critical impact on drug metabolism. Also, uremic toxins can impact by accumulating and competing with the drugs for hepatic metabolization or hepatic transportation in the cells. Finally, cytochrome P450 activity may be modified by CKD, too [9, 10].

Uremia may also alter the distribution of drugs, especially in the presence of critical changes in the patient’s hydration state [9, 10].

Moreover, CKD is associated with an increased risk of thromboembolic events. Renal failure is characterized by disorders of the coagulation cascade and activation of the fibrinolytic system, decreased platelet activity, and impaired vessel-wall–platelet interactions [11].

Clinical guidelines are available for handling drugs in CKD patients. Depending on the GFR value, drug dose decrease or modulation might be needed. Also, certain drugs should be avoided because of a lack of evidence or the correlated bleeding risk [12].

How can we estimate renal function in cancer patients?

Algorithms for estimating GFR based on creatinine dosage are available, like the sMDRD formula or the CKD-Epi formula. Unfortunately, no specific formula for GFR exists today for cancer patients, even though it is known that this population’s creatinine levels might be altered. Currently, the best approach is to use one of the standard algorithms considering the patient’s specific condition.

Another evaluation consists of analyzing microalbuminuria and proteinuria in the urine sample. The presence of cells in the urine should also be evaluated.

Watch Corinne Bagnis’s lecture:

References

1. Hill NR, Fatoba ST, Oke JL, et al. Global Prevalence of Chronic Kidney Disease – A Systematic Review and Meta-Analysis. PLoS One. 2016;11(7):e0158765. Published 2016 Jul 6. doi:10.1371/journal.pone.0158765
2. Launay-Vacher V, Oudard S, Janus N, et al. Prevalence of Renal Insufficiency in cancer patients and implications for anticancer drug management: the renal insufficiency and anticancer medications (IRMA) study. Cancer. 2007;110(6):1376-1384. doi:10.1002/cncr.22904
3. Launay-Vacher V. Epidemiology of chronic kidney disease in cancer patients: lessons from the IRMA study group. Semin Nephrol. 2010;30(6):548-556. doi:10.1016/j.semnephrol.2010.09.003
4. Janus N, Launay-Vacher V, Byloos E, et al. Cancer and renal insufficiency results of the BIRMA study. Br J Cancer. 2010;103(12):1815-1821. doi:10.1038/sj.bjc.6605979
5. Canter D, Viterbo R, Kutikov A, et al. Baseline renal function status limits patient eligibility to receive perioperative chemotherapy for invasive bladder cancer and is minimally affected by radical cystectomy. Urology. 2011;77(1):160-165. doi:10.1016/j.urology.2010.03.091
6. Launay-Vacher V, Spano JP, Janus N, et al. Renal insufficiency and anticancer drugs in elderly cancer patients: a subgroup analysis of the IRMA study. Crit Rev Oncol Hematol. 2009;70(2):124-133. doi:10.1016/j.critrevonc.2008.09.012
7. Na SY, Sung JY, Chang JH, et al. Chronic kidney disease in cancer patients: an independent predictor of cancer-specific mortality. Am J Nephrol. 2011;33(2):121-130. doi:10.1159/000323740
8. Breton G, Froissart M, Janus N, et al. Inappropriate drug use and mortality in community-dwelling elderly with impaired kidney function–the Three-City population-based study. Nephrol Dial Transplant. 2011;26(9):2852-2859. doi:10.1093/ndt/gfq827
9. Launay-Vacher V, Storme T, Izzedine H, Deray G. Modifications pharmacocinétiques au cours de l’insuffisance rénale [Pharmacokinetic changes in renal failure]. Presse Med. 2001;30(12):597-604
10. Vanholder R, De Smet R, Glorieux G, et al. Review on uremic toxins: classification, concentration, and interindividual variability [published correction appears in Kidney Int. 2020 Nov;98(5):1354]. Kidney Int. 2003;63(5):1934-1943. doi:10.1046/j.1523-1755.2003.00924.x
11. Potpara TS, Ferro CJ, Lip GYH. Use of oral anticoagulants in patients with atrial fibrillation and renal dysfunction. Nat Rev Nephrol. 2018;14(5):337-351. doi:10.1038/nrneph.2018.19
12. Chen A, Stecker E, A Warden B. Direct Oral Anticoagulant Use: A Practical Guide to Common Clinical Challenges. J Am Heart Assoc. 2020;9(13):e017559. doi:10.1161/JAHA.120.017559
13. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130(6):461-470. doi:10.7326/0003-4819-130-6-199903160-00002