Changes in Glomerular Filtration Rate and Impact on Long-Term Survival among Adults after Hematopoietic Cell Transplantation: A Prospective Cohort Study

Clin J Am Soc Nephrol. 2018 Jun 7;13(6):866-873. doi: 10.2215/CJN.10630917. Epub 2018 Apr 18.

Abstract

Background and objectives: Kidney injury is a significant complication for patients undergoing hematopoietic cell transplantation (HCT), but few studies have prospectively examined changes in GFR in long-term survivors of HCT. We described the association between changes in GFR and all-cause mortality in patients up to 10 years after HCT.

Design, setting, participants, & measurements: We conducted a prospective, observational cohort study of adult patients undergoing HCT at the Fred Hutchinson Cancer Center in Seattle, Washington from 2003 to 2015. Patients were followed from baseline, before conditioning therapy, until a maximum of 10 years after transplant. We used Cox proportional hazard models to examine the association between creatinine eGFR and all-cause mortality. We used time-dependent generalized estimating equations to examine risk factors for decreases in eGFR.

Results: A total of 434 patients (median age, 52 years; range, 18-76 years; 64% were men; 87% were white) were followed for a median 5.3 years after HCT. The largest decreases in eGFR occurred within the first year post-transplant, with the eGFR decreasing from a median of 98 ml/min per 1.73 m2 at baseline to 78 ml/min per 1.73 m2 by 1 year post-HCT. Two thirds of patients had an eGFR<90 ml/min per 1.73 m2 at 1 year after transplant. When modeled as a continuous variable, as eGFR declined from approximately 60 ml/min per 1.73 m2, the hazard of mortality progressively increased relative to a normal eGFR of 90 ml/min per 1.73 m2 (P<0.001). For example, when compared with an eGFR of 90 ml/min per 1.73 m2, the hazard ratios for eGFR of 60, 50, and 40 ml/min per 1.73 m2 are 1.15 (95% confidence interval, 0.87 to 1.53), 1.68 (95% confidence interval, 1.26 to 2.24), and 2.67 (95% confidence interval, 1.99 to 3.60), respectively. Diabetes, hypertension, acute graft versus host disease, and cytomegalovirus infection were independently associated with a decline in GFR, whereas calcineurin inhibitor levels, chronic graft versus host disease, and albuminuria were not.

Conclusions: Adult HCT recipients have a high risk of decreased eGFR by 1 year after HCT. Although eGFR remains fairly stable thereafter, a decreased eGFR is significantly associated with higher risk of mortality, with a progressively increased risk as eGFR declines.

Keywords: Adult; Behavior Therapy; Calcineurin Inhibitors; Graft versus Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Proportional Hazards Models; Survivors; Washington; albuminuria; creatinine; diabetes mellitus; glomerular filtration rate; hypertension; kidney; kidney dysfunction; mortality; risk factors.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Female
  • Glomerular Filtration Rate*
  • Graft vs Host Disease / etiology
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / mortality*
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Renal Insufficiency, Chronic / etiology
  • Young Adult