Abstract

The kidney is one of the most sensitive organs to cadmium-induced toxicity, particularly in conditions of long-term oxidative stress. We hypothesized that, in kidney transplant recipients, nephrotoxic exposure to cadmium represents an overlooked hazard for optimal graft function. To test this, we performed a prospective cohort study and included 672 outpatient kidney transplant recipients with a functioning graft of beyond one year. The median plasma cadmium was 58 ng/L. During a median 4.9 years of follow-up, 78 kidney transplant recipients developed graft failure with a significantly different distribution across tertiles of plasma cadmium (13, 26, and 39 events, respectively). Plasma cadmium was associated with an increased risk of graft failure (hazard ratio 1.96, 95% confidence interval 1.56-2.47 per log(2) ng/L). Similarly, a dose-response relationship was observed over increasing tertiles of plasma cadmium, after adjustments for potential confounders (donor, recipient, transplant and lifestyle characteristics), robust in both competing risk and sensitivity analyses. These findings were also consistent for kidney function decline (graft failure or doubling of serum creatinine). Thus, plasma cadmium is independently associated with an increased risk of long-term kidney graft failure and decline in kidney function. Further studies are needed to investigate whether exposure to cadmium represents an otherwise overlooked modifiable risk factor for adverse long-term graft outcomes in different populations.

Original languageEnglish
Pages (from-to)1213-1224
Number of pages12
JournalKidney International
Volume99
Issue number5
Early online date14-Sep-2020
DOIs
Publication statusPublished - May-2021

Keywords

  • cadmium
  • kidney function decline
  • kidney transplant recipients
  • long-term graft failure
  • oxidative stress
  • tubular damage
  • PROGRESSIVE DIABETIC-NEPHROPATHY
  • ENVIRONMENTAL LEAD-EXPOSURE
  • RENAL DYSFUNCTION
  • CHELATION-THERAPY
  • OXIDATIVE STRESS
  • BLOOD CADMIUM
  • UNITED-STATES
  • HYPERTENSION
  • BIOMARKERS
  • SURVIVAL

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