An accurate assessment of kidney function prior to hematopoietic cell transplantation

An accurate assessment of kidney function prior to hematopoietic cell transplantation (HCT) can help to properly dose conditioning chemotherapy and follow patients for the development of chronic kidney disease. bedside CKiD formulas showed significant bias (95% confidence interval) overestimating the nuclear GFR by 57.4 (49.0-65.8) and 14.1 (7.1-21.1) ml/min/1.73m2 MLN2238 respectively. Cystatin C formulas had less mean bias and improved accuracy but also had decreased sensitivity to detect abnormal kidney function prior to HCT. The Full CKiD equation showed the best performance with a mean bias of ?3.6 (?8.4-1.2) ml/min/1.73m2 that was not significantly different from the measured value and 87.7% of estimates within ±30% of the nuclear GFR. While the more recent bedside CKiD formula performed better than the original Schwartz formula both formulas had poor sensitivity for detecting MLN2238 a low GFR. An abnormal pre-transplant nuclear GFR was not associated with post-HCT acute kidney injury the need for dialysis or death in the first 100 days. In conclusion we observed cystatin C-based equations outperformed creatinine-based equations in estimating GFR in children prior to HCT. However all formulas had decreased sensitivity to detect impaired GFR. Formal measurement of kidney function should be considered in children and young adults who need an accurate assessment of kidney function prior to HCT. Keywords: kidney function transplant pediatrics cystatin C INTRODUCTION Chronic kidney disease (CKD) occurs in at least 15% of patients after hematopoietic cell transplantation HCT [1]. Certain chemotherapeutic agents used for conditioning prior to HCT need to be dose-adjusted depending on the glomerular filtration rate (GFR) [2]. Following transplant an accurate assessment of GFR is needed to dose other medications MLN2238 including antibiotics and calcineurin inhibitor therapy for graft versus host disease (GVHD) prophylaxis as well as to monitor patients over time for the development of CKD [3]. Outside of research protocols there are no established guidelines for how to assess kidney function (GFR) before HCT. Available options include serum creatinine 24 hour urine collections for creatinine clearance and formal MLN2238 measurements of GFR using an injected nuclear isotope or contrast agent such as iohexol. Some have suggested that a pre-HCT serum creatinine ≤1.5 mg/dL and MLN2238 a creatinine clearance >60 ml/min are favored prior to starting transplant [4]. While creatinine may have a limited ability to Hhex estimate GFR in patients with low muscle mass formal GFR testing is more costly invasive and time consuming [3 5 We reported that cystatin C was more accurate than creatinine in estimating GFR in 16 children receiving autologous HCT [6]. Unlike serum creatinine cystatin C may be impartial of muscle mass but possibly affected by other non-renal factors such as corticosteroid treatment or body weight [5 7 Cystatin C has been less studied in patients undergoing HCT [8-12]. Our objective was to expand on our prior work by examining GFR in a larger cohort of children and young adults before HCT which included allogeneic recipients. We used the most recent estimating equations recommended by the 2012 Kidney Disease Improving Global Outcomes (KDIGO) consensus guidelines [13] and focused on comparing creatinine-estimated GFR to a measured nuclear GFR and secondarily included cystatin C-estimated GFR. MATERIALS and METHODS Study population We conducted a cross-sectional analysis of children and young adults who were enrolled in a prospective cohort originally designed to study risk factors for thrombotic microangiopathy after HCT. The cohort included 100 consecutive children and young adults receiving a HCT at Cincinnati Children’s Hospital Medical Center (CCHMC) from September 2010 to December 2011. Of these 100 subjects 95 had a nuclear GFR performed for clinical indications prior to transplant. Two autologous recipients have been reported in our prior study [6]. Clinical data were recorded from the medical record and included age gender primary diagnosis race height MLN2238 weight exposure to prior chemotherapy number of prior HCT (if any) corticosteroid therapy prior to transplant and creatinine and blood urea nitrogen values. We also.