Pseudoxanthoma elasticum is a rare disease mainly due to ABCC6 gene mutations and characterized by ectopic biomineralization and fragmentation of elastic fibers resulting in skin, cardiovascular and retinal calcifications. It has been recently described that pyrophosphate (a calcification inhibitor) deficiency could be the main cause of ectopic calcifications in this disease and in other genetic disorders associated to mutations of ENPP1 or CD73. Patients affected by Pseudoxanthoma Elasticum seem also prone to develop kidney stones originating from papillary calcifications named Randall’s plaque, and to a lesser extent may be affected by nephrocalcinosis. In this narrative review, we summarize some recent discoveries relative to the pathophysiology of this mendelian disease responsible for both cardiovascular and renal papillary calcifications, and we discuss the potential implications of pyrophosphate deficiency as a promoter of vascular calcifications in kidney stone formers and in patients affected by chronic kidney disease.

Arterial calcification is a common feature of pseudoxanthoma elasticum (PXE), a disease characterized by ABCC6 mutations, inducing a deficiency in pyrophosphate, a key inhibitor of calcium phosphate crystallization in arteries. Methods: we analyzed whether long-term exposure of Abcc6^−/− mice (a murine model of PXE) to a mild vitamin D supplementation, with or without calcium, would impact the development of vascular calcification. Eight groups of mice (including Abcc6^−/− and wild-type) received vitamin D supplementation every 2 weeks, a calcium-enriched diet alone (calcium in drinking water), both vitamin D supplementation and calcium-enriched diet, or a standard diet (controls) for 6 months. Aorta and kidney artery calcification was assessed by 3D-micro-computed tomography, Optical PhotoThermal IR (OPTIR) spectroscopy, scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM-EDS) and Yasue staining. Results: at 6 months, although vitamin D and/or calcium did not significantly increase serum calcium levels, vitamin D and calcium supplementation significantly worsened aorta and renal artery calcification in Abcc6^−/− mice. Conclusions: vitamin D and/or calcium supplementation accelerate vascular calcification in a murine model of PXE. These results sound a warning regarding the use of these supplementations in PXE patients and, to a larger extent, patients with low systemic pyrophosphate levels.

Trauma‐induced calcification is the pathological consequence of complex injuries which often affect the central nervous system and other parts of the body simultaneously. We demonstrated by an animal model recapitulating the calcification of the above condition that adrenaline transmits the stress signal of brain injury to the calcifying tissues. We have also found that although the level of plasma pyrophosphate, the endogenous inhibitor of calcification, was normal in calcifying animals, it could not counteract the acute calcification. However, externally added pyrophosphate inhibited calcification even when it was administered after the complex injuries. Our finding suggests a potentially powerful clinical intervention of calcification triggered by polytrauma injuries which has no effective treatment.

Lithium poisoning could trigger multiple complications. We report the case of a lithium poisoning with five complications that are described for the first time together. A 60-year-old woman was admitted in our intensive care unit for altered consciousness. Severe lithium intoxication was diagnosed (lithium plasmatic level 8.21 mmol/l) associated with acute oliguric kidney failure. Continuous renal replacement therapy was started immediately. Orotracheal intubation was quickly required because of status epilepticus. Medullary aplasia happened 48 h after the patient was intubated. Infectious and immunological causes were ruled out and lithium poisoning was considered as the most likely etiology. Iterative blood and platelet transfusion were required. Severe polyneuropathy was diagnosed on the 5th day after admission. The patient showed a peripheral tetraparesia and cranial nerve failure while lithium plasmatic level had decreased to a therapeutic level. Conversely, urine output increased and hypernatremia promptly occurred, which led to diabetes insipidus diagnosis. Neuropathy decreased in 72 h and the patient was definitely extubated by the 11th day. Hematologic disturbances decreased and no blood transfusion would be required after the 8th day. The patient would keep sequellas of the poisoning. Thin motricity would still be altered and polyuria would remain. Diffuse alopecia was promptly observed, with no iron deficiency or thyroid disturbance. In addition to presenting this case report, we herein discuss the drug causality, the consequences, and the plausible pathophysiology of these five situations.