Predictive biomarkers of hypercalciuria in patients with permanent postsurgical hypoparathyroidism. Clinical implications

Resumen

Hypercalciuria is an adverse event of postsurgical hypoparathyroidism treatment which can lead to nephrolithiasis, nephrocalcinosis and renal insufficiency. The collection of 24-hour urine is often considered an unreliable method to detect hypercalciuria. The objective of the study was to find useful predictive biomarkers of hypercalciuria in patients with permanent postsurgical hypoparathyroidism receiving treatment with oral calcium and calcitriol supplements. We performed a prospective cross-sectional study in an outpatient hospital clinical setting. A total of 42 consecutive stable patients with postsurgical hypoparathyroidism taking oral calcium and calcitriol supplements, and 17 adult controls without hypoparathyroidism, were included. The main outcome measure was hypercalciuria, defined as 24-hour urine calcium above 300 mg. Results: As expected, of the variables compared between controls and patients, only those that were related to the hypoparathyroid condition showed significant differences (calcium supplements, calcitriol dosage, serum parathyroid hormone, and urinary calcium excretion). Patients without hypercalciuria (n=26) vs. those with hypercalciuria (n=16) had lower levels of serum 1,25-dihydroxyvitamin D (32.4+11.7 pg/ml vs. 45.8+9.3 pg/ml; p<0.001), lower albumin-corrected serum calcium (8.42+0.46 mg/dl vs. 8.73+0.48 mg/dl; p=0.047), and similar serum parathyroid hormone levels (12.7+5.4 pg/ml vs. 11.2+7.4 pg/ml; p:ns). Multiple linear regression analysis showed a significant independent relationship between 1,25-dihydroxyvitamin D and urinary calcium excretion (B= 7.566+1.679; p<0.001). A cut-off value of 33.5 pg/ml for serum 1,25-dihydroxyvitamin D to predict the absence of hypercalciuria had 100% sensitivity and 65.4% specificity, and the area under the ROC curve was 0.829. No patients with serum 1,25-dihydroxyvitamin D under 33.5 pg/ml presented hypercalciuria, regardless of the level of albumin-corrected serum calcium. Five patients with hypercalciuria, albumin-corrected serum calcium level above 8.5 mg/dl, and serum levels of 1,25-dihydroxyvitamin D above 33.5 pg/ml, were treated by having their vitamin D3 supplements and calcitriol doses reduced, without thiazide diuretics being added. They normalized their urinary calcium excretion, and their serum 1,25-dihydroxyvitamin D levels were simultaneously lowered to less than 33.5 pg/ml. Conclusions: Serum 1,25-dihydroxyvitamin D is a useful biomarker to predict the absence of hypercalciuria in patients with permanent postsurgical hypoparathyroidism who are receiving treatment with oral calcium and calcitriol supplements. The measurement of serum 1,25-dihydroxyvitamin D will permit us to limit the measurement of 24-hour urine calcium to those patients with serum levels of 1,25-dihydroxyvitamin D above 33.5 pg/ml. We propose an algorithm based on the monitorization of serum 1,25-dihydroxyvitamin D that will improve the clinical management of patients with postsurgical hypoparathyrodism that are receiving supplementary treatment.