P1634TIME-UPDATED SERUM CALCIUM AND PHOSPHATE ARE ASSOCIATED WITH GRAFT AND PATIENT OUTCOMES AFTER KIDNEY TRANSPLANTATION
Authors: Van der Plas Willemijn , Gomes-Neto António W , Berger Stefan P , Kruijff Schelto , Bakker Stephan , De Borst Martin 
Published: June 2020

Abstract

Background and Aims
Disturbances in calcium-phosphate homeostasis are common after kidney transplantation. The clinical implications of changes in calcium-phosphate homeostasis after transplantation are unclear. The aim of this study was to assess the relationship between time-updated serum calcium and phosphate levels and subsequent graft and patient outcomes.

Method
Kidney transplant recipients with ≥2 serum calcium and phosphate measurements were included from a large single-center cohort; only first transplants were considered. Patients with graft failure &lt;3 months were excluded, as were measurements obtained when eGFR was &lt;15 mL/min/1.73m2 or during intensive care unit admission. Normocalcemia was defined as (albumin-corrected) calcium between 2.20 and 2.60 mmol/L (8.8-10.4 mg/dL), and normophosphatemia as 0.70-1.50 mmol/L (2.17-4.64 mg/dL). Time-updated multivariable Cox regression analyses and time-updated restricted cubic splines analyses were performed to assess the relationship between post-KTx serum corrected calcium and phosphate levels and mortality and death-censored graft failure (DCGF). Final models were adjusted for recipient age, sex, BMI, eGFR, proteinuria, systolic BP (all time-updated), antihypertensive drug use, recipient CMV status, donor age, sex, and status (living or post-mortal), cold and warm ischemia times, HLA mismatches, primary kidney disease, and serum phosphate (in calcium analyses) or corrected calcium (in phosphate analyses).

Results
A total of 2,769 patients with 138,496 serum corrected calcium and phosphate levels post-KTx were included (median [IQR] 43 [31-61] measurements per patient). Mean age was 47 ± 14 yrs, 42.3% was female, and 19% underwent a pre-emptive transplantation. Hypercalcemia was more common in the first year (15%) and declined to ∼5% during long-term follow-up; hypocalcemia occurred in ∼10% throughout. Hypophosphatemia (24.3%) and hyperphosphatemia (15.5%) were particularly common during the first 30 days post-transplant, and stabilized at ∼10% and ∼5% after the first year. During median follow-up of 16.3 (8.7 – 25.2) years, 477 patients (17.2%) developed DCGF and 1050 (37.9%) patients died. In multivariable regression analyses, post-transplant hypocalcaemia was associated with an increased risk of DCGF (fully adjusted hazard ratio [HR] 2.01 [95% CI 1.61-2.50], P&lt;0.0001; Figure 1A), but not mortality (HR 1.06 [95% CI 0.88-1.27], P=0.55; Figure 1B). Post-transplant hypercalcaemia was associated with an increased risk of mortality (HR 1.77 [95% CI 1.44-2.17], P&lt;0.0001), but not DCGF (HR 0.79 [95% CI 0.48-1.32], P=0.37). Patients with post-KTx hyperphosphatemia were at increased risk of both DCGF (HR 37.12 [95% CI 30.33-45.42], P&lt;0.0001; Figure 1C) and mortality (HR 3.17 [95% CI 1.65-3.86], P&lt;0.0001; Figure 1D). Patients with hypophosphataemia had a lower risk of developing DCGF (HR 0.48 [95% CI 0.28-0.81], P&lt;0.01), but not mortality (HR 0.92 [95% CI 0.72-1.18], P=0.42). Similar results were obtained in sensitivity analyses in a subgroup with parathyroid hormone data available (N=1,412) or after exclusion of the highest and lowest 0.5% of calcium or phosphate levels.

Conclusion
Post-transplant hypocalcaemia and hyperphosphatemia are associated with an increased risk of DCGF, while hypophosphataemia was linked with a lower DCGF risk. Hypercalcaemia and hyperphosphataemia were associated with an increased mortality risk. These findings underline the relevance of keeping calcium and phosphate within normal range after kidney transplantation.