Determinants of Hypercalciuria and Renal Calcifications in Chronic Hypoparathyroidism

Abstract and Introduction

Abstract

Objective: Hypercalciuria, impaired kidney function and renal calcifications are common in chronic hypoparathyroidism (HypoPT). We aimed to study associations between indices of known importance to the kidney in HypoPT by hypothesizing adverse effects of hypercalciuria on renal outcomes.

Design: We used cross-sectional design.

Patients: We identified all patients followed for chronic HypoPT at our department and who had been examined by a 24-h urine collection for measurement of renal calcium excretion (24 h U-Ca).

Measurements: By chart review, we identified additional biochemistry measured in close connection with the collection of urine, as well as demographic, treatments and anthropometrics.

Results: The 166 included patients (79.5% females) had a high prevalence of hypercalciuria (65.7%). In multiple adjusted analyses, hypercalciuria was in an independent manner inversely associated with (residual) levels of plasma PTH and positively associated with levels of 1,25-dihydroxyvitamin D and ionized calcium as well as 24 h U-phosphate, gender, and etiology (surgical vs. non-surgical). Overall, this model explained 54% (p < .001) of the variation in the presence of hypercalciuria. Chronic kidney disease stage three or above was present in 18.3% of the patients, and 42.6% of the 54 patients examined by renal imaging had renal calcifications. However, neither renal function nor renal calcifications were associated with 24 h U-Ca.

Conclusions: Hypercalciuria, impaired renal function and renal calcifications are common in hypoparathyroidism. Hypercalciuria is to a large extent explained by indices of known physiological importance to 24 h U-Ca. However, in the present study, a high renal calcium excretion did not explain renal impairment or kidney calcifications.

Introduction

Hypoparathyroidism (HypoPT) is a rare endocrine disease, which causes hypocalcaemia due to missing or inappropriately low plasma levels of parathyroid hormone (P-PTH).^[1] In most instances, the disease emerges following neck surgery, which causes damage to the parathyroid glands. However, in approximately one-fourth of the patients, the disease is due to non-surgical causes, including genetic variants and autoimmunity.^[2] Due to lack of PTH, the renal 1α-hydroxylase (CYP27B1) is not well-stimulated resulting in a reduced synthesis of 1,25-dihydroxyvitamin D (1,25(OH)₂D), which impairs intestinal calcium absorption. Accordingly, HypoPT is a two-hormone deficiency state with too low levels of both PTH and 1,25(OH)₂D. Lack of both hormones results in a dysregulation of the calcium-phosphate homeostasis. Hypocalcaemia emerges as a consequence of reduced intestinal calcium absorption. Moreover, urinary calcium is often elevated, as there is no stimulation by PTH of the renal tubular reabsorption of calcium. The disease is also characterized by relatively high plasma levels of phosphate, as the renal phosphate excretion is impaired.^[3] Despite relatively low calcium levels, the calcium-phosphate (CaxP) product is often increased in HypoPT. Both post-surgical and non-surgical HypoPT are conventionally treated similarly using active vitamin D (alfacalcidol or calcitriol) and calcium supplements. However, despite a (near-) normalization of plasma calcium with this treatment, patients are at increased risk of several complications, including impaired renal function, nephrolithiasis and nephrocalcinosis.^[4] Although it seems likely that the increased risk of kidney diseases is attributable to disturbances in calcium-phosphate homeostasis, no studies have so far been able to establish the importance of, for example, hypercalciuria, hyperphosphataemia, or different doses of active vitamin D and calcium supplements. In the present study, we therefore identified all patients followed at our department with chronic HypoPT who had been examined with a 24-h (24 h) urine collection for measurement of renal calcium excretion in order to investigate associations between biochemistry, kidney diseases, demographic, treatments and anthropometrics. Our main hypothesis was that hypercalciuria is of major importance in the development of renal calcifications and impaired kidney function.