Impact of Acute Kidney Injury Following Diagnosis of Aggressive Lymphoma or Acute Leukemia on Long-Term Kidney Outcomes

Acute kidney injury (AKI) is common in those with newly diagnosed hematologic malignancies. Precipitants of AKI in this population may include tumor lysis syndrome, hypotension and other insults associated with acute illness. In a general population, AKI not only leads to short-term consequences like fluid, electrolyte and acid-base abnormalities, but each episode has been linked to worse long-term outcomes, including chronic kidney disease, cardiovascular events and death. In patients with malignancies, loss of kidney function may be additionally detrimental, as this can jeopardize eligibility for full dose or first line chemotherapy, transplantation or enrollment in clinical trials. The purpose of this study is to determine the impact of AKI on long-term loss of kidney function in patients newly diagnosed with aggressive lymphomas or acute leukemia.

We performed a population-based cohort study using data from the Rochester Epidemiology Project (REP). The REP is a medical-record linkage system that integrates data for patients across multiple medical care providers in Olmsted County, MN and surrounding areas to facilitate long-term follow-up. Adults admitted to the hospital between 2005 and 2017 following a new diagnosis of acute leukemia or aggressive lymphoma were evaluated for the exposure of AKI. AKI was defined by the KDIGO serum creatinine (SCr) criterion (Stage 1: 1.5-fold increase from baseline or 0.3mg/dL increase in 48-hours; Stage 2: 2-fold increase from baseline; Stage 3: 3-fold increase from baseline, increase in SCr to >4mg/dL, or initiation of renal replacement therapy). Only the first episode of hospitalization was included. Cox proportional hazards regression was used to compare the primary outcome of loss of kidney function within 12 months of hospitalization [defined as ≥30% decline from baseline estimated glomerular filtration rate (eGFR)] in those with and without AKI. A subgroup analysis was performed in patients with a baseline eGFR <60 mL/min/1.73m². eGFR calculations used the Chronic Kidney Disease Epidemiology Collaborative equation. Outcome evaluation began 90-days after hospitalization to establish chronicity and was defined only by outpatient SCr values.

Within the REP cohort, 1,085 patients were hospitalized following a new diagnosis of acute leukemia or lymphoma who consented to the use of their medical records for research. Sixteen patients with pre-existing end-stage renal disease were excluded, leaving 1,069 included patients for analysis. The majority were white (n=1,002; 93.7%) males (n=624; 58.4%) with a mean (SD) age of 64 (18) years. Mean baseline SCr was 1.0 (0.4) mg/dL with a corresponding eGFR of 80 (27) ml/min/1.73m². A total of 355 patients (33.2%) experienced AKI during the index hospitalization, most commonly a maximum stage of I (n=231; 21.6%). Stages II and III AKI occurred in 42 (3.9%) and 59 (5.5%) patients, respectively. Cumulative incidence of ≥30% loss of baseline eGFR in the 12 months following hospitalization was 67.9% (95% CI 56.8%-76.1%) for those with any AKI and 38.8% (95% CI 31.8%-45.1%) for those without AKI during the index hospitalization. Patients diagnosed with any stage AKI were more likely to experience this outcome compared to those without AKI (HR 2.6, 95% CI 2.2-3.5, p<0.001) in unadjusted analysis. Amongst those with a baseline eGFR ≤60 ml/min, no significant difference in the outcome was noted (HR 1.7, 95% CI 0.83-3.35, p=0.15).

Patients with AKI during initial hospitalization following a new diagnosis of acute leukemia or aggressive lymphoma were significantly more likely to experience ≥30% loss of baseline eGFR in the 12 months following diagnosis. This highlights a critical need to identify interventions which prevent AKI and optimize renal recovery so as to decrease overall morbidity and preserve eligibility for desirable treatment options.