Hypoalbuminemia and not undernutrition predicts high‐dose methotrexate‐induced nephrotoxicity in children with acute lymphoblastic leukemia in resource‐constrained centers

Abstract

Background:The standard practice to mitigate high-dose methotrexate (HD-MTX)induced nephrotoxicity (HMN) in acute lymphoblastic leukemia (ALL) is to monitor levels until serum MTX falls below a predefined threshold. It is not feasible in most resource-constrained centers. Literature on the various factors affecting HMN in these centers is limited, retrospective, and heterogeneous. Though hypoalbuminemia has been postulated as a risk factor for HMN, the relationship of undernutrition with HMN has not been studied.Procedure: This prospective observational study consecutively enrolled children < 12 years old with ALL receiving HD-MTX. Children with preexisting renal disease and exposed to nephrotoxic drugs two weeks preceding HD-MTX infusion were excluded.HD-MTX was administered over 24 hours (BFM-2009 protocol) with 12 hours of prehydration. Solitary MTX levels at 36 hours (MTX36) were outsourced, and 6-8 doses of leucovorin were given six-hourly. Hydration was continued till last dose of leucovorin.Various factors affecting HMN (rise in creatinine to 1.5 times baseline) were recorded: age, sex, type of ALL, risk group of ALL, first dose of MTX, dose of MTX, undernourishment, serum protein, and albumin along with C-reactive protein and MTX36 levels.Results: Forty-four children who received 150 HD-MTX cycles were analyzed. HMN was seen in 14% of cycles. On univariate analysis, undernourishment, MTX36 levels, hypoproteinemia, and hypoalbuminemia were significantly associated with HMN. On multivariate analysis, hypoalbuminemia and MTX36 levels significantly predicted the development of HMN with odds ratios of 4.71 and 1.45. Conclusion: Hypoalbuminemia and solitary serum MTX levels predict HMN in centerswhere serial MTX level monitoring is not feasible.

Development of a novel nomogram for predicting delayed methotrexate excretion following high-dose methotrexate in adult patients with hematologic malignancies

“…Despite the establishment of optimal supportive care, HDMTX poses the risk of devastating complications. HDMTX-induced nephrotoxicity typically occurs in approximately 10% cases, [17,20,23] with single studies reporting nephrotoxicity rates as high as 38%. [30] These adverse effects pose a greater challenge to adult patients with lymphoma, who are commonly over 70 years of age and have multiple comorbidities.…”

“…Moreover, previous studies on HDMTX have predominantly focused on pediatric and adolescent patients with acute lymphoblastic leukemia (ALL) or osteosarcoma. [8,9,[17][18][19] Even studies involving elderly cohorts often include a mix of lymphoma and solid tumors, [5,10,13,20,21] which compromises the direct application of ndings to these more vulnerable populations. For instance, con icting results have been reported regarding MTX concentration and renal function, with no relationship reported only in childhood ALL.…”

Influence of Hypoalbuminemia on Methotrexate Clearance in Children Receiving High Dose Methotrexate Therapy

“…There was no statistically significant difference in adverse effects seen between the two groups, with the exception of cases with renal impairment. 17 Khera et al concluded that hypoalbuminemia and solitary serum MTX levels predict HDMTX-induced nephrotoxicity in centers where serial MTX level monitoring is not feasible. 18 Mohassel et al conducted another trial on 510 cases and found that there were 204 adult patients and 106 pediatric patients.…”