Creatinine > 1.5 Mg/Dl and MDS Diagnosis Predicts Poor Outcome Following HSCT
Authors: Martin Fern , Mikkilineni Lekha , Parikh Kinjal , Grosso Dolores , Leiby Benjamin E , Alpdogan Onder , Carabasi Matthew , Kasner Margaret , Klumpp Thomas R. , Martinez-Outschoorn Ubaldo , Sharma Manish , Weiss Mark , Wagner John L. , Flomenberg Neal , Filicko-O'Hara Joanne 
Published: October 2019

Abstract
Introduction
Acute renal failure (ARF) after hematopoietic stem cell transplantation (HSCT) is an important complication associated with transplant-related mortality (TRM). In the first 100 days after HSCT, ARF can be secondary to other major complications, such as sepsis, sinusoidal obstruction syndrome, acute graft-versus-host disease (GVHD), and viral reactivation.ARF also occurs in the setting of nephrotoxic drugs, such as amphotericin B,and calcineurin inhibitors. We hypothesize that risk factors for ARF after HSCT include pre-transplant comorbidities, such as chronic kidney disease (CKD), acute kidney injury (AKI) prior to HSCT and hypertension. Mortality is greater in patients with ARF after HSCT than those without ARF. When ARF requires hemodialysis (HD), the mortality rate rises to greater than 80%. The aim of this study was to identify prognostic indicators for the development of ARF requiring HD or leading to death within 100 days after HSCT.
Methods
We performed a retrospective analysis of patients undergoing allogeneic HSCT at Thomas Jefferson University Hospital to identify prognostic indicators for poor outcomes after HSCT. We analyzed data for all patients who underwent allogeneic HSCT between the years of 2004-2014. After initial analysis, we excluded subjects who had diagnoses for which there were less than twenty patients. Univariate analysis was performed to identify risk factors for ARF requiring HD, 30-day mortality and 100-day mortality. Univariate association of categorical variables with outcomes and potential confounding variables was assessed using exact Chi-square tests. All variables associated with outcomes with p<0.2 were entered into a logistic regression model with the final model being selected using a backward elimination procedure until all variables had p<0.2.
Results
We analyzed 373 consecutive patients who underwent allogeneic HSCT at our institution between 2004 and 2014. After excluding diagnoses with less than twenty patients, we analyzed the remaining 332 patients. Median age was 54 years (range 19-78) and 42% of subjects were female. Diagnoses included acute myeloid leukemia (44.3 %), non-Hodgkin lymphoma (22.3%), acute lymphoid leukemia (14.8 %), myelodysplastic syndrome (MDS) (11.8%) and multiple myeloma (6.9%). Univariate associations between risk factors and three outcomes- renal failure requiring HD, 30-day mortality and 100-day mortality, were assessed. Within this set of 332 subjects, the incidence of renal failure requiring HD was 11.8%., 30-day mortality was 6.3%, and 100-day mortality was 16.6%.
Creatinine >1.5 mg/dL at the time of HSCT was significantly associated with these outcomes. In addition, the diagnosis of MDS was associated with both 100-day mortality (p <0.001) and HD (p =0.0091). An increase in creatinine by 50% or greater between the time of admission and the day of HSCT was associated with need for HD (p =0.0026). Final logistic regression models show that candidate variables for predicting 30-day mortality were creatinine >1.5 mg/dL on the day of HSCT (p =0.045), use of amphotericin (p =0.052), and diagnosis of MDS (p =0.11). Candidate variables for predicting 100-day mortality were creatinine >1.5 mg/dL on the day of (p =0.023), diagnosis of MDS (p =0.035), and each one year increase in age (p =0.013). Candidate variables for renal failure requiring HD were creatinine >1.5 mg/dL on the day of HSCT (p <0.001) and a diagnosis of MDS (p =0.03). Creatinine at HSCT and diagnosis were included in all models.
Discussion
Although preexisting renal disease is incorporated into current models of risk at the time of transplant (e.g. HCT-CI), the specific risk for HD has not previously been quantified. Our analysis shows an 11.8% risk of ARF requiring HD following HSCT, with increased risk related to preexisting renal disease and underlying diagnosis of MDS. This suggests that patients should be counseled appropriately about this specific risk of renal failure requiring HD if the creatinine is >1.5 mg/dL. Similarly, patients with creatinine >1.5 mg/dL at time of HSCT are also at increased risk of 30-day and 100-day mortality compared to their counterparts with creatinine ≤1.5.

Disclosures
No relevant conflicts of interest to declare.