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 <3 months were excluded, as were measurements obtained when eGFR was <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<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<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<0.0001; Figure 1C) and mortality (HR 3.17 [95% CI 1.65-3.86], P<0.0001; Figure 1D). Patients with hypophosphataemia had a lower risk of developing DCGF (HR 0.48 [95% CI 0.28-0.81], P<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.
Allostatic Load, Unhealthy Behaviors, and Depressive Symptoms by Birthplace Among Older Adults in the Sacramento Area Latino Study on Aging (SALSA)
