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.