Estimation versus measurement of the glomerular filtration rate for kidney function assessment in patients with cancer undergoing cisplatin-based chemotherapy

Abstract

Glomerular filtration rate (GFR) assessment is indicated before every administration of cisplatin. The optimal modality for this purpose [GFR measurement by urinary Creatinine Clearance (uCrCl) versus GFR estimation (eGFR) by the CKD-EPI formula versus both] is unclear. We investigated whether eGFR only is safe in this setting. Paired uCrCl and eGFR determinations from 470 cisplatin cycles from 121 patients were analyzed [median age: 55 years; most frequent tumor site: genitourinary (45%); palliative treatment: n = 41 (34%)]. Primary endpoint was the proportion of cycles with uCrCl < 50 ml/ min/1.73m 2 and eGFR ≥ 50 ml/min/1.73m 2 (i.e. a "false negative" result when only determining eGFR). The primary endpoint occurred in 8 of 470 cisplatin cycles (1.7%, 95%CI 0.5-2.9). In all 8 events, uCrCl was lower than eGFR (mean uCrCl vs. eGFR: 43 versus 112 ml/min/1.73m 2). The uCrCl was re-measured in all patients, and showed normal results in all but 1 patient. None of these events precluded the administration of cisplatin at the planned date, and no subsequent cases of acute nephrotoxicity occurred. Overall agreement between uCrCl and eGFR was low, with qualitative analysis suggesting frequent incompliance with 24-h urine collection. We conclude that an eGFR is sufficient for assessing kidney function in patients with cancer undergoing cisplatin therapy. Cisplatin is a widely-used antineoplastic drug that is essential for the therapy of a broad range of solid and hematologic cancers in children 1 , adolescents 2 , and adults 3,4. Acute kidney injury (AKI) is a rare but potentially life-threatening complication of cisplatin therapy 5. Because this complication occurs predominantly in patients with already pre-existing kidney dysfunction, cisplatin is widely considered to be contraindicated in patients with a glomerular filtration rate (GFR) below 50-60 ml/min/1.73m 26,7. To identify these patients, a pre-treatment evaluation of kidney function by determining the GFR is mandatory in every patient before every cisplatin administration 8. However, it is unclear which method of GFR assessment is optimal for this purpose, with some centers opting for (1) a GFR measurement by urinary Creatinine Clearance (uCrCl), (2) an estimated GFR by a validated formula such as CKD-EPI (eGFR), or (3) both 9. The uCrCl has the advantage of being the potentially most accurate routinely-available method of GFR assessment ("gold standard", ignoring non-routinely available

NLRP3 Inflammasome: A Promising Therapeutic Target for Drug-Induced Toxicity

“…Therefore, drug-induced toxicity is a vital problem in drug development and clinical drug application (Björnsson, 2016;Onakpoya et al, 2016). The use of many common drugs is limited by drug-induced organ injury, such as statins (Bouitbir et al, 2020), rifampicin (Chen et al, 2017), anthracyclines (Avila et al, 2018), and cisplatin (Klockl et al, 2020). Moreover, some drugs considered very safe can cause organ damage when they are taken in too high a dose or when idiosyncratic reaction occurs (Larson et al, 2005;Matsuo et al, 2014).…”

The Onco-Nephrology Field: The Role of Personalized Chemotherapy to Prevent Kidney Damage

“…In a recent study, Klockl et al concluded that it is useful to evaluate the renal function with only eGFR (namely omitting the burdensome timed urine collection for CrCl measurement) for patients with solid cancers who have received at least one cycle of cisplatin therapy ( Table 4 ) [ 121 ].…”

Estimation of kidney function for medication dosing in adult patients with chronic kidney disease: a practice update

“…45 Studies in cancer settings have shown eCrCl to be less reliable than the other equations when used by the bedside for dosage selection for kidney-excreted anticancer medications when compared with the use of mGFR. 26,47 In line with the newly developed International Consensus Guideline for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) by eviQ and Cancer Institute NSW, it is recommended to use eGFR CKD-EPI as the standard and routine estimate of kidney function, and to use BSA-adjusted eGFR CKD-EPI for carboplatin dosing using the Calvert equation. 46 The ADDIKD was developed after an extensive and in-depth review of published literature.…”

“…The underestimate was demonstrated using inulin for gold standard GFR determination. 47 The ongoing changes in kidney function duration gestation and post-partum also make it difficult to predict steady state, limiting the usefulness of eGFR further. 64 Serial serum creatinine concentrations are recommended for monitoring kidney function in pregnancy, especially in acute illness.…”

“…carboplatin dosing) 45 . Studies in cancer settings have shown eCrCl to be less reliable than the other equations when used by the bedside for dosage selection for kidney‐excreted anticancer medications when compared with the use of mGFR 26,47 …”