Acute kidney injury in cancer patients

Wim Van Biesen for

Norbert LameireEm prof of MedicineUniversity Hospital

Gent, Belgium

Tbilisi, october 2015

Cumulative incidence (risk) of AKI during the first 5 years after a cancer diagnosis

Christiansen et al. / European J Int Med 22 (2011) 399–406

37,267 incident cancer patients -5yrs FU

9613 (25.8%) developed AKI

1-yr risk:17.5% 5-yr risk: 27.0%

mortality

RI

F

The timing of AKI, presented as percentages of total AKI against days after admission to the

cancer center.

Salahudeen et al, Clin J Am Soc Nephrol 8: 347–354, 2013.

* 12% of all admissions to cancer center over 3 month period had AKI* Most cases seen in recent admissions

Main associated factors of AKI in cancer patients(n: 309)

Soares et al, J Clin Oncol 24:4003-4010, 2006

Kaplan-Meyer survival curve for 90 days after admission to the cancer center based on AKI severity by RIFLE

Salahudeen et al, Clin J Am Soc Nephrol 8: 347–354, 2013

Length of hospital stay

Hospital bills

Salahudeen et al, Clin J Am Soc Nephrol 8: 347–354, 2013

Length of hospital stay

Hospital bills

Salahudeen et al, Clin J Am Soc Nephrol 8: 347–354, 2013

Large confidence intervals

Effect of AKI on outcomes of cancer patients

Campbell et al, Adv CKD, 2014, 21: 64-71

Anticancer therapies requiring dosage adjustment as a percentage of prescriptions

(A) and as a percentage of treated patients (B).

Launay-Vacher et al, Cancer 2007;110:1376–1384.

S crea = 1.5: what about renal function???

Patient-specific factors that increase risk for chemotherapy- asssociated nephrotoxicity

Shirali, Perazella, Adv CKD , 2014, 21: 56-63,

Categories of chemotherapy-Induced nephrotoxicity

Perazella, Moeckel, Semin Nephrol 30:570-581, 2010

Pathophysiology of cisplatinum nephrotoxicity

Pabla N, Dong Z. Kidney Int 73: 994–1007, 2008.

Magnesium supplementation in prevention of cisplatinum nephrotoxicity

Kidera et al, PLoS ONE 9(7): e101902., 2014

Comparison of cis-platin with its Second and Third Generation Platinum Analogues

Ali et al , Anti-Cancer Agents in Medicinal Chemistry, 2013, 13, 296-306

Purine metabolism- uric acid is the endproduct in humans

Wilson, Berns Adv CKD, 2014, 21: 18-26

The Cairo-Bishop Definitions of laboratory and clinical Tumor Lysis Syndrome

Wilson, Berns Adv CKD, 2014, 21: 18-26

Reported incidences of TLS stratified by Risk Category

Wilson, Berns Adv CKD, 2014, 21: 18-26

Flowchart of patients included in thestudy according to the presence of TLS

Darmon et al, British Journal of Haematology, 2013, 162, 489–497

Prophylaxis and Treatment of Tumor Lysis Syndrome

Denker et al, European J Int Med 22 (2011) 348–354

Only 1 RCT 7 observational historical control

Risk of AKI associated with androgen deprivation therapy for advanced prostate

cancer (observational)

Lapi et al , JAMA. 2013;310(3):289-296.

Cumulative incidence plot depicting the rates of AKI after stratifying patients according to the type of androgen deprivation for non metastatic prostate Ca

(gonadotropin releasing agonists)

Gandaglia et al, EUROPEAN UROLOGY 66 (2014) 1125–1132

Mechanisms of FLCs-induced kidney injury

Davenport, Merlini, Nephrol Dial Transplant (2012) 27: 3713–3718

Probability of renal recovery following sustained reduction in free light chain levels at day 21 in myeloma kidney.

Hutchison et al. J. Am. Soc. Nephrol. 22, 1129–1136 © 2011

Combination of bortezomib-based chemotherapy and extracorporeal free light chain removal for

treating cast nephropathy in MM-2 cases

Bachmann et al, NDT Plus (2008) 2: 106–108

Figure 2. Forest plot of weighted risk ratio comparing 6-month survival rate between chemotherapy withplasmapheresis and chemotherapy only group.

International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 5/2015 (391-397)

Figure 3. Forest plot of weighted risk ratio comparing 6-month dialysis-dependent rate between chemotherapy with plasmapheresis and chemotherapy only group.

International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 5/2015 (391-397)

Novel approaches for reducing free light chains in patients with myeloma kidney

Hutchison, C. A. et al. Nat. Rev. Nephrol. 8, 234–243 (2012 )

General conclusions• Be aware of renal probems in patients with cancer• Acute Kidney Injury• Chronic Kidney injury• Keep it simple:• rehydration• dose-adaptation• most “exciting new promising” therapies NOT

supported by evidence