Article
Renal impairment in hypophosphatasiaAtteinte rénale des hypophosphatasies

https://doi.org/10.1016/S0929-693X(18)30023-XGet rights and content

Summary

Renal impairment in hypophosphatasia (HPP) has been described but remains poorly understood: hypercalciuria, nephrocalcinosis and sometimes even chronic kidney failure secondary to chronic hypercalcemia/hypercalciuria or exposure to toxic agents. The objectives of this review are to describe the different renal lesions observed in HPP, and the therapeutic measures that can be applied (in particular, thiazide diuretics).

Résumé

L’atteinte rénale des hypophosphatasies (HPP) existe, mais est, en réalité, peu connue : hypercalciurie, néphrocalcinose et parfois même insuffisance rénale chronique après hypercalcémie/hypercalc iurie ou après exposition à des toxiques. L’objectif de cette mise au point est d’envisager les différentes atteintes rénales possibles en cas d’HPP et les moyens de les prendre en charge (en particulier les diurétiques thiazidiques).

Introduction

Renal impairment in HPP has been described but remains poorly understood: hypercalciuria, nephrocalcinosis and sometimes even chronic renal failure in a context of hypercalcemia/hypercalciuria or exposure to toxic agents (non-steroidal anti-inflammatory drugs, bisphosphonates). Renal impairment occurs in the early-onset severe cases of HPP as defined by Whyte et al., in patients with clinical signs emerging before age 6 months [1]. In a Japanese series of 52 patients with HPP, only three presented with renal calcifications although all of them presented with the lethal perinatal disease [2]. In the large American series of 173 children, renal impairment was unfortunately not evaluated [3].

With regard to pathophysiology, at least in the early infantile forms of the disease, skeletal mineralization is blocked by extracellular accumulation of inorganic pyrophosphate. This results in hypercalcemia (classically considered absorptive, but probably secondary to a disequilibrium between bone resorption and an abnormal bone mineralization), which may or may not be associated with hypercalciuria, during which parathyroid hormone (PTH) levels become low, in an adaptive manner [1]. In the HPP forms diagnosed later in life, the metabolic abnormalities are much milder; blood calcium, vitamin D and PTH levels are normal [1]. Patients nonetheless present with a tendency toward hyperphosphatemia with increased tubular phosphate reabsorption (increase in maximum rate of phosphate reabsorption, TmP/GFR) [4], whose exact mechanisms have yet to be elucidated [1]. The objective of this review is to consider the various potential renal impairments in the event of HPP and the resources for their management.

Section snippets

Literature review

Table 1 summarizes the publications on HPP that report on renal impairment and its management. The underlying mechanisms and courses are addressed in the publications publishing isolated clinical cases by Barcia et al. [5], Auron et al. [6], Baumgartner-Sigl et al. [7], Mohn et al. [8], Whyte et al. [4], and Cundy et al. [9].

Implications for practice

In practice, in the absence of any etiological treatment, the following conclusions may be drawn from the clinical cases:

1/ management should aim at decreasing intestinal calcium absorption (in particular, a low diet, including low calcium milk, Locasol®; limitation of endogenous 1,25-vitamin D production, corticosteroids) is sometimes effective in early onset HPP, but should be avoided as far as possible since there is a long-term risk of an additional negative effect on bone mineralization;

2/

Conclusion and prospects

In the future, long-term studies to generate additional data on renal impairment would be of value even though the latter is not the primary concern in patients with HPP [10].

Statements of interests

No interests.

No financial aid.

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