Post-Transplant Hypophosphatemia and the Risk of Death-Censored Graft Failure and Mortality after Kidney Transplantation

Clin J Am Soc Nephrol. 2017 Aug 7;12(8):1301-1310. doi: 10.2215/CJN.10270916. Epub 2017 May 25.

Abstract

Background and objectives: Hypophosphatemia is common in the first year after kidney transplantation, but its clinical implications are unclear. We investigated the relationship between the severity of post-transplant hypophosphatemia and mortality or death-censored graft failure in a large cohort of renal transplant recipients with long-term follow-up.

Design, setting, participants, & measurements: We performed a longitudinal cohort study in 957 renal transplant recipients who were transplanted between 1993 and 2008 at a single center. We used a large real-life dataset containing 28,178 phosphate measurements (median of 27; first to third quartiles, 23-34) serial measurements per patient) and selected the lowest intraindividual phosphate level during the first year after transplantation. The primary outcomes were all-cause mortality, cardiovascular mortality, and death-censored graft failure.

Results: The median (interquartile range) intraindividual lowest phosphate level was 1.58 (1.30-1.95) mg/dl, and it was reached at 33 (21-51) days post-transplant. eGFR was the main correlate of the lowest serum phosphate level (model R2 =0.32). During 9 (5-12) years of follow-up, 181 (19%) patients developed graft failure, and 295 (35%) patients died, of which 94 (32%) deaths were due to cardiovascular disease. In multivariable Cox regression analysis, more severe hypophosphatemia was associated with a lower risk of death-censored graft failure (fully adjusted hazard ratio, 0.61; 95% confidence interval, 0.43 to 0.88 per 1 mg/dl lower serum phosphate) and cardiovascular mortality (fully adjusted hazard ratio, 0.37; 95% confidence interval, 0.22 to 0.62) but not noncardiovascular mortality (fully adjusted hazard ratio, 1.33; 95% confidence interval, 0.9 to 1.96) or all-cause mortality (fully adjusted hazard ratio, 1.15; 95% confidence interval, 0.81 to 1.61).

Conclusions: Post-transplant hypophosphatemia develops early after transplantation. These data connect post-transplant hypophosphatemia with favorable long-term graft and patient outcomes.

Keywords: Cardiovascular Diseases; Confidence Intervals; Follow-Up Studies; Humans; Hypophosphatemia; Longitudinal Studies; Phosphates; Proportional Hazards Models; Regression Analysis; Renal Insufficiency, Chronic; Risk; chronic kidney disease-mineral and bone disorder; graft survival; hypophosphatemia; kidney transplantation; mortality; phosphate; transplantation.

MeSH terms

  • Adult
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / mortality*
  • Cause of Death
  • Chi-Square Distribution
  • Female
  • Follow-Up Studies
  • Graft Survival
  • Humans
  • Hypophosphatemia / diagnosis
  • Hypophosphatemia / etiology
  • Hypophosphatemia / mortality*
  • Kidney Transplantation / adverse effects
  • Kidney Transplantation / mortality*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Proportional Hazards Models
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome