INTRODUCTION
Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer with an annual incidence of 30 cases per million persons younger than 20 in the United States.1,2 The cure rate of ALL has improved from less than 10% in the 1960’s to around 90% in recent decades with innovations in chemotherapy, bone marrow transplantation (BMT), and better supportive care1,3. However, with improvement in cure rate, there has been increased emergence of long-term therapy related complications such as musculoskeletal morbidity, cardiac comorbidities (congestive heart failure, coronary artery disease) and neurological comorbidities (cranial nerve palsy, cognitive defects)3. While there are several studies that address the prevalence of renal dysfunction and hypertension in children diagnosed and successfully treated for ALL, most of these studies investigated subjects with onset of disease prior to 2010.4-15
Children diagnosed with ALL are at risk for renal injury due to a number of factors including 1) intrinsic renal injury, secondary to either leukemic cell lysozyme induced direct tubular damage, leukemic infiltration, tumor lysis syndrome, sepsis, and/or exposure to nephrotoxic medications, 2) prerenal acute kidney injury from volume depletion, secondary to poor oral intake, vomiting and diarrhea, and 3) thrombotic microangiopathies. 4,16 Studies from prior decades reported that 10-30% of survivors of childhood ALL have persistent reduced glomerular filtration rates (GFR).4,6,7
To more thoroughly understand renal injury, beyond assessing kidney function (GFR), presence of persistent proteinuria and albuminuria can indicate glomerular and/or tubular injury, and persistent proteinuria has been well documented as a major risk factor for the progression of renal disease17. To our knowledge, urine protein/creatinine and urine microalbumin/creatinine have not been previously reported in children with a history of ALL.
Hypertension (HTN), cardiovascular disease, and metabolic syndrome are known complications in patients who are long-term survivors of ALL.9,12,18,19 This has been attributed to multiple factors, including renal leukemic infiltration, persistent reduced glomerular filtration rate (GFR), chemotherapy, fluid overload, and exposure to chronic increased sodium loads from intravenous fluids and especially high dose steroids.10,11,20 Prior studies from the 1990’s and 2000’s show wide variation in incidence of HTN in children with ALL ranging from 5-65%, depending on timing of blood pressure (BP) measurement and definition of HTN.5,10,15,20,21 The latest clinical practice guideline for screening and management of high blood pressure in children and adolescents recommends obtaining a 24-hour ambulatory BP monitoring (ABPM) study in all children prior to establishing the diagnosis of hypertension.22 ABPM studies can help uncover “white coat HTN” (related to anxiety in clinical settings), masked HTN (normal office BP readings with elevated 24 hour mean BP), nocturnal HTN and abnormal nocturnal BP dipping (incomplete or absent decrease in BP while sleeping compared to while awake). To date, there has been only one study using ABPM in pediatric patients with ALL to assess for HTN23.
The aim of this study was to determine the prevalence of 1) persistent renal dysfunction based on assessments of GFR, proteinuria, and microalbuminuria and 2) HTN using in-clinic BP values and ABPM in children with ALL, at one to five years after ALL diagnosis.