P0655CIRCULATING 1,25-DIHYDROXYVITAMIN D AND ITS RATIO WITH 1-84PTH ARE PREDICTORS OF WORSENING RENAL FUNCTION IN CKD3 PATIENTS
Authors: Galassi Andrea , Fasulo Eliana Maria , Hawkins Douglas M , Cozzolino Mario Gennaro 
Published: June 2020

Abstract

Background and Aims
The variable deterioration of patients with chronic kidney disease poses an omnipresent need for improved renal care management. At present, renal function in CKD patients is measured or estimated using the glomerular filtration rate (mGFR and eGFR). While mGFR affords the most objective and accurate evaluation of kidney function, it is not routinely used for repeated assessment due to its expense and difficulty to execute. Although eGFR provides the most diffuse approach for the monitoring of renal function, its commonality does not come without limitations: above 60mL/min*1.73m2, serum creatinine, and therefore eGFR variability are increasingly impacted by muscle metabolism/mass, age, gender, diet and fluid imbalances. eGFR can neither anticipate nor predict kidney damage.
In CKD, deficiency of 1,25-dihydroxyvitamin D (1,25(OH)2D) develops during the progression of kidney failure, due to the decreased capability of renal proximal tubule cells to mediate the final hydroxylation step of 25-hydroxyvitamin D to 1,25(OH)2D. While not measured routinely in the clinic, new methods make the measurement of 1,25(OH)2D possible and reliable, and data on its performance as a biomarker are emerging.
The aim of this study is to describe the ability of the LIAISON® XL 1,25 Dihydroxyvitamin D measurement to predict worsening renal function in conjunction with other relevant analytes.

Method
This monocentric study was observational, prospective and descriptive, with a longitudinal approach. 71 patients were assessed for mGFR determination by 99mTc-diethylenetriamine-pentaacetic acid at baseline. Twenty percent worsening of renal function, based on eGFR, provided the primary endpoint which was evaluated at 3 and 6 months. In addition, serum levels of 1,25(OH)2D, 25(OH)D, 1-84 PTH, intact FGF23, sclerostin, alkaline phosphatase (bone-specific and total) and calcium/phosphorus along with 24h urine levels of creatinine, phosphorus, calcium and sodium were measured. Endpoint analyses were performed by receiver operating characteristics, univariate, and multivariate logistic regressions.

Results
ROC analyses of 1,25(OH)2D and the 1,25(OH)2D/1-84PTH ratio for patients with early CKD (stage 3) showed very good performance in predicting worsening of renal function with AUCs of 0.916 (p&lt;0.0001, criterion ≤29 pg/mL) and 0.791 (p&lt;0.0005, criterion ≤0.844), respectively. Significance was lost for both markers’ outcome prediction with CKD4 subjects. Of interest, endpoint prediction by 1,25(OH)2D was also better in all patients &lt;70 years old (AUC=0.883. p&lt;0.0001). In univariate logistic regression analysis, 1,25(OH)2D is the single and strongest predictor of WRF (p=0.0029) corroborating the ROC analysis. In backward-elimination multi-variate regression, the 1,25(OH)2D/1-84PTH ratio and 1-84PTH are the final variables in the regression model (p=0.00013). Interestingly, while the ratio correlates well with mGFR (R=0.541), 1,25(OH)2D does not (R=0.116).

Conclusion
1,25(OH)2D and the ratio of 1,25(OH)2D/1-84PTH are strong predictors of outcome in CKD3 patients, and thus these measurements may indicate improved clinical care for this important class of patients. Further research of these biomarkers is needed to expand the observations to larger numbers and more diverse populations.