Prevalence, Treatment, and Outcomes of Renal
Conditions in Pediatric Sickle Cell Disease
James R. Stallworth, MD, Avnish Tripathi, MD, MPH, and Jeanette M. Jerrell, PhD
Objectives: Vaso-occlusive events in pediatric sickle cell disease
(SCD) may cause various renal complications and lead to renal failure.
We describe the renal conditions that develop among young patients
with SCD and the factors associated with the prevalence of these
nephropathies.
Materials and Methods: Medicaid medical and pharmacy claims
for an 11-year period were used to identify 2194 pediatric patients
with SCD (HbSS homozygous). Survival analysis identified the most
significant predictors of acute kidney injury and chronic renal fail-
ure, using demographics, SCD severity and pain medication, comor-
bid hypertension, hematuria, and proteinuria as the initial covariates.
Results: Prevalence of renal complications in our cohort was found
to be relatively low, predominantly hematuria (6.3%) and proteinuria
(3.2%). The multivariable analysis indicated that earlier development
of acute kidney injury was significantly associated with older age (ad-
justed hazard ratio [aHR] 1.16, confidence interval [CI] 1.06Y1.27),
preexisting hypertension (aHR 3.05, CI 1.09Y8.60), and preexisting
hematuria (aHR 2.87, CI 1.05Y7.93). Earlier development of chronic
renal failure was significantly associated with older age (aHR 1.20, CI
1.08Y1.32), preexisting hematuria (aHR 4.67, CI 1.57Y13.94), and
preexisting proteinuria (aHR 8.25, CI 2.12Y10.38).
Conclusions: These prevalence findings are novel in the US SCD
pediatric population. The predictors of nephropathies identified in
these children confirm clinical expectations. In addition, they suggest
not only that pediatric nephrologists should be consulted earlier in
the treatment of patients with SCD who are diagnosed as having co-
morbid hypertension or who develop hematuria or proteinuria during
the course of their SCD treatment but also that both hydroxyurea and
angiotensin-converting enzyme inhibitor therapies may be better used
in these cases.
Key Words: kidney conditions, pediatrics, outcomes, sickle cell
disease
P
atients with sickle cell disease (SCD; HbSS) may present
with a wide spectrum of renal dysfunction. In patients
with SCD, relative hypoxia in the renal medulla and slow
blood flow through the vasa rectae predisposes red blood
cells to sickling, resulting in significant veno-occlusion and
subsequent local infarction.
1Y3
The early manifestations of
sickle cell nephropathy include impaired urinary concentrating
ability; supranormal proximal tubular function manifested by
a mild degree of hypophosphatemia and increased clearance
of creatinine; and defects in both urinary acidification and
potassium excretion.
1,3
With increasing age and additive tu-
bulointerstitial nephritis secondary to analgesic overuse, renal
abnormalities may progress to manifestations such as hema-
turia, proteinuria, papillary necrosis, glomerulonephritis, and
acute and chronic renal failure.
1Y4
The present hypothesized
model of sickle cell nephropathy suggests that destruction
of the renal medulla and resulting hyperfiltration may lead to
Key Points
& The prevalence of renal disease in a cohort of US children
with sickle cell disease (HbSS) is examined. The results
confirm that earlier development of various nephropathies
was associated with diagnosis of primary hypertension, he-
maturia, or proteinuria during the course of treatment for
HbSS.
& There appears to be some underutilization of hydroxyurea
(HU) and angiotensin-converting enzyme inhibitors (ACE-Is)
in children with HbSS and renal abnormalities.
& No significant association was found between nonsteroidal
anti-inflammatory drug treatment and the development of
any form of nephropathy in children with HbSS taking into
consideration all other significant influences.
Original Article
752 * 2011 Southern Medical Association
From the Departments of Pediatrics and Neuropsychiatry and Behavioral
Science, University of South Carolina School of Medicine, and the De-
partment of Epidemiology and Biostatistics, University of South Carolina
Arnold School of Public Health, Columbia, South Carolina.
Reprint requests to Dr Jeanette M. Jerrell, Department of Neuropsychiatry
and Behavioral Science, University of South Carolina School of Med-
icine, 3555 Harden Street, Suite 301, Columbia, SC 29203. Email:
Jeanette.Jerrell@uscmed.sc.edu
The views expressed in the article do not represent official findings of the
South Carolina Department of Health and Human Services (Medicaid).
The authors have no financial relationships to disclose and no conflicts of
interest to report.
Accepted July 27, 2011.
Copyright * 2011 by The Southern Medical Association
0038-4348/0Y2000/104-752
DOI: 10.1097/SMJ.0b013e318232d9ab
Copyright © 2011 The Southern Medical Association. Unauthorized reproduction of this article is prohibited.