Discussion
In this study, we add to the small but important body of literature by
evaluating the relationship between pre-SCT hyperfiltration, renal
morbidity, and mortality. We found that pre-SCT GFR≥135 mL/min per 1.73
m2 was not associated with AKI, 1 year event-free
survival, or CKD at a median follow up time of 4.7 years.
Glomerular hyperfiltration is a well described phenomenon in physiologic
states, such as pregnancy and high protein intake, as well as many
pathologic states, including diabetes mellitus, hypertension,
hyperaldosteronism, and obesity.7 Hyperfiltration has
also been noted in 30 – 40 % of children with cancer at diagnosis
and/or during initial stages of their chemotherapy, however the
mechanisms driving the elevation in GFR in these patients poorly
understood.3,8
One population in which hyperfiltration is a known phenomenon and may
undergo SCT is patients with sickle cell disease. Hyperfiltration has
been identified in half of young adults with sickle cell
disease.9 In a series of 18 pediatric patients with
sickle cell disease undergoing nonmyeloablative SCT, 12/18 had a
measured GFR and 8/18 had an creatinine based estimated GFR greater than
150 mL/min/1.73 m2 prior to transplant. After SCT,
overall GFR declined in the entire population with just 4/18
hyperfiltrating. One interpretation of this data is that the glomeruli
can functionally normalize with resolution of the hematopoietic disease.
An alternative hypothesis that the GFR declined due to AKI and it will
continue to decline as seen in CKD. Similarly, a publication looking at
kidney function in children after SCT showed a similar, and
statistically significant decline from hyperfiltration to normal GFR in
the first two years post-SCT.11 Median pre-SCT
measured by inulin clearance was 130 ml/min/1.73m2(73-127 ml/min/1.73m2), at 1 year was 123
ml/min/1.73m2 (68–185
ml/min/1.73m2), and at 2 years was 105
ml/min/1.73m2 (81–177
ml/min/1.73m2). Since the GFR decline is from elevated
to normal, the changes are not captured in standard clinical and
survivorship screening.
An additional limitation to understanding the epidemiology and
implications of hyperfiltration in SCT patients is the lack of a uniform
definition. A systematic review of over 400 studies showed numerous,
variable thresholds applied, ranging from 90.7 to 175
ml/min/1.73m2.6 Method of GFR
calculation is also of critical importance, as creatinine has been shown
to be a less reliable biomarker in pediatric SCT
patients.12,13 For this study, we used measured
nuclear medicine GFRs with an a priori cut off of 135
ml/min/1.73m2 because it is the median value in the
literature.6 Using this threshold, there was no
association between any demographic and hyperfiltration, nor between
hyperfiltration and any outcomes. However, this threshold may be too low
for the pediatric SCT population. Age- and sex-matched control groups
may be necessary to define the hyperfiltration thresholds in this group.
Multiple thresholds of increasing GFR, like the stages of increasing AKI
severity, may be more informative than a single threshold.
Further research is needed to determine whether a different threshold
for hyperfiltration would have prognostic value. Long-term follow up
focused on hyperfiltrating patients to assess long term risk of CKD is
also warranted.