Kidney Week

Abstract: FR-PO915

High Plasma Cadmium and Late Graft Failure in Renal Transplant Recipients

Session Information

• Transplantation: Translational and Transplant Pathology
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 1802 Transplantation: Clinical

Authors

• Vodegel, Joppe J., University Medical Center Groningen, Groningen, Netherlands

Joppe J. Vodegel,

• Eisenga, Michele F., University Medical Center Groningen, Groningen, Netherlands

Michele F. Eisenga,

• Knobbe, Tim J., University Medical Center Groningen, Groningen, Netherlands

Tim J. Knobbe,

• Lammerts, Rosa G.m., University Medical Center Groningen, Groningen, Netherlands

Rosa G.m. Lammerts,

• De Borst, Martin H., University Medical Center Groningen, Groningen, Netherlands

Martin H. De Borst,

• Berger, Stefan P., University Medical Center Groningen, Groningen, Netherlands

Stefan P. Berger,

• Nolte, Ilja M., University Medical Center Groningen, Groningen, Netherlands

Ilja M. Nolte,

• Touw, Daniel J., University Medical Center Groningen, Groningen, Netherlands

Daniel J. Touw,

• Bakker, Stephan J.L., University Medical Center Groningen, Groningen, Netherlands

Stephan J.L. Bakker,

Background

Although short-term outcome after kidney transplantation has strongly improved, late graft failure remains a major distress for both patient and physician, and its etiology is poorly understood. This urges the identification of new treatable risk factors for late graft failure. In the general population, substantially increased plasma cadmium levels contribute to progressive renal function loss. Since renal transplant recipients (RTRs) only have one functioning kidney which is also exposed to noxious factors during transplantation, we assumed that RTRs are more susceptible to cadmium nephrotoxicity. Therefore, we hypothesized that higher plasma cadmium levels, even below the normal range, are associated with an increased risk of graft failure in RTRs.

Methods

The study was conducted in the TransplantLines Food and Nutrition Biobank cohort study. Plasma cadmium was measured using inductive coupled plasma mass spectrometry (ICP-MS). All RTRs (age>18 years) had a functioning graft for more than one year. Cox regression analyses were used to investigate prospective associations of cadmium with graft failure.

Results

We included 706 RTRs (age 53±13 years; 56.8% males at mean 5.4 (1.9-12.0) years after transplantation). Mean plasma cadmium levels were 0.70 ± 0.13 µg/L (normal range <5 µg/L) and eGFR was 45.0 ± 18.7 ml/min/1.73m² (normal range 90 – 120 ml/min/1.73m²). During follow-up for 4.9 (3.3-5.5) years, 80 (11.3%) RTRs developed graft failure. In univariable analysis, increased plasma cadmium levels were associated with increased risk of graft failure (hazard ratio (HR) 2.49 [95%CI 1.73-3.58], P < 0.001). In multivariate analysis, after adjustment for age, sex, proteinuria, primary renal disease, time since transplantation, acute rejection, cold ischemia time, HLA mismatches, deceased donor status, BMI, systolic blood pressure, plasma glucose, diabetes, smoking, and alcohol use, the association of cadmium with graft failure remained (HR 2.23 [1.39-3.57], P = 0.001).

Conclusion

We conclude that cadmium levels are associated with an increased risk of graft failure in RTRs. Interventions aiming at reducing bodily cadmium concentrations, e.g. chelation therapy, seem warranted to improve long-term graft survival after renal transplantation.

Funding

• Government Support - Non-U.S.