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.