Renal Function and Low–Molecular-Weight Proteins (Cystatin C, b 2 -Microglobulin, Neutrophil Gelatinase-associated Lipocalin) in Child and Young Adult Cancer Survivors Joanna Stefanowicz, MD, PhD,* Rados!aw Owczuk, MD, PhD,w Ewa Aleksandrowicz, MD, PhD,z Anna Owczarzak, MD, PhD, z Andrzej Kurylak, MD, PhD, y Elz ˙ bieta Adamkiewicz-Droz ˙ yn ´ska, MD, PhD, * and Anna Balcerska, MD, PhD* Background: We sought to verify the hypothesis that children and young adults with cancer who have completed treatment differ according to the type and degree of renal damage. Procedure: This study included 144 children and young adults (73 female) who had completed treatment for leukemias and lym- phomas (group L, n = 45), Wilms tumor (group W, n = 52) and other solid tumors (group S, n = 47). The following parameters were evaluated: serum concentrations of creatinine, cystatin C, b 2 -microglobulin, neutrophil gelatinase-associated lipocalin and urine excretion of albumin, and urinalysis with sediment. Glomerular filtration rate (eGFR) was estimated using the classic Schwartz (eGFR Sch ), Schwartz redux (eGFR Schred ), and Filler (eGFR Filler ) formulas and with the new Schwartz equation for patients with chronic kidney disease (eGFR SchCKD ). Results: Group S had the lowest eGFR SchCKD and eGFR Filler , the highest serum cystatin C and the highest albumin excretion com- pared with groups L and W. Groups S and W had lower eGFR Sch and eGFR Schred and higher serum b 2 -microglobulin and neutrophil gelatinase-associated lipocalin compared with group L. Group W had lower eGFR SchCKD than group L. Conclusions: Children and young adults with cancer who have completed treatment differ in the type and degree of renal damage they sustain. Key Words: childhood neoplasms, survivors, late effects, renal function, nephrotoxicity (J Pediatr Hematol Oncol 2012;34:461–466) R ecent years have brought significant improvements in treatment outcomes for childhood malignancies. The increasing number of cancer survivors necessitates mon- itoring for the long-term consequences of antineoplastic treatment. Cancer is listed among the risk factors for chronic kidney disease (CKD) (http://www.kidney.org/ professionals/KDOQI/guidelines_ckd/p4_class_g3.htm). It is generally accepted that severe chronic kidney injury after cytostatic treatment is rather rare. Subclinical kidney injury is described more often. It is also known that CKD can be a sequela of anticancer treatment. 1 The recent introduction of the term “CKD” and its diagnostic criteria by the National Kidney Foundation (NKF; http://www.kidney.org/professionals/KDOQI/guide lines_ckd/p4_class_g1.htm) 2 provides a new perspective on the follow-up of children after oncological treatment. Kidney function monitoring in these patients allows the early diagnosis of CKD and the implementation of appropriate treatment. Pediatric oncology patients form a heterogenous group with differing neoplasm diagnoses, types of anticancer treatments and side effects. Children diagnosed with nephroblastoma com- prise a unique group because the majority of them are left with a single kidney after treatment. Patients with solid tumors are the second group at risk of renal damage caused by potentially nephrotoxic chemotherapy. Children diagnosed with acute lymphoblastic leukemia are the group most in danger of developing acute kidney injury during intensive chemotherapy. Kidney damage in this group may be caused by neoplastic infiltration of the kidney or tumor lysis syndrome, or they may experience kidney damage as secondary effect of chemotherapy and adjuvant treatment. 3 Glomerular filtration rate (GFR) is the classical para- meter of kidney function. According to the NKF, for clinical purposes, the estimated glomerular filtration rate (eGFR) in children should be evaluated using Schwartz classic formula, which is based on the serum creatinine (Cr) concentration and the child’s height (http://www.kidney.org/professionals/ KDOQI/guidelines_ckd/p5_lab_g4.htm). 4 Recently, Schwartz and colleagues published new, more accurate formulas to estimate GFR in children with mild to moderate renal func- tion impairment. The first is a 5-variable equation that in- cludes height and sex, blood urea nitrogen (BUN) levels, serum cystatin C concentration (Cys C), and serum Cr con- centration. The second is a “simplified, bedside” prediction equation that differs from the classic constant k value (k = 0.413). 5,6 Renal function is difficult to monitor because many oncological patients have signs of subclinical kidney injury. The search for kidney function biomarkers has continued for many years. Over the last decade, low–molecular-weight proteins (LMWPs), such as Cys C, neutrophil gelatinase- associated lipocalin (NGAL) and b 2 -microglobulin (b 2 M), have drawn the most attention. Although eGFR is the basic Received for publication June 15, 2011; accepted March 29, 2012. From the Departments of *Pediatrics, Hematology, Oncology, Endocrinology; wAnesthesiology and Intensive Therapy; zClinical Nutrition and Laboratory Diagnostics, Medical University of Gdansk; and yDepartment of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland. The authors declare no conflict of interest. Reprints: Joanna Stefanowicz, MD, PhD, Department of Pediatrics, Hematology, Oncology, Endocrinology, Medical University of Gdansk, 7 Debinki Street, 80-952 Gdansk, Poland (e-mail: jstefanowicz@gumed.edu.pl). Copyright r 2012 by Lippincott Williams & Wilkins CLINICAL AND LABORATORY OBSERVATIONS J Pediatr Hematol Oncol  Volume 34, Number 6, August 2012 www.jpho-online.com | 461