Hypercalcemia is common during Pneumocystis pneumonia in kidney transplant recipients

Abstract

A few cases of hypercalcemia related to Pneumocystis jirovecii pneumonia (PJP) have previously been described, supposedly associated with an 1α-hydroxylase enzyme-dependent mechanism. The prevalence and significance of hypercalcemia in PJP remain unclear, especially in kidney transplant recipients (KTR) who frequently display hypercalcemia via persisting hyperparathyroidism. We here retrospectively identified all microbiologically-proven PJP in adult KTR from 2005 to 2017 in the Lille University Hospital, and studied the mineral and bone metabolism parameters during the peri-infectious period. Clinical features of PJP-patients were analyzed according to their serum calcium level. Hypercalcemia (12.6 ± 1.6 mg/dl) was observed in 37% (18/49) of PJP-patients and regressed concomitantly to specific anti-infectious treatment in all cases. No other cause of hypercalcemia was identified. In hypercalcemic patients, serum levels of 1,25-dihydroxyvitamin D were high at the time of PJP-diagnosis and decreased after anti-infectious treatment (124 ± 62 versus 28 ± 23 pg/mL, p = 0.006 ) while PTH serum levels followed an inverse curve (35 ± 34 versus 137 ± 99 pg/mL, p = 0.009 ), suggesting together a granuloma-mediated mechanism. Febrile dyspnea was less frequent in hypercalcemic PJP-patients compared to non-hypercalcemic (29 versus 67%). In summary, hypercalcemia seems common during PJP in KTR. Unexplained hypercalcemia could thus lead to specific investigations in this particular population, even in the absence of infectious or respiratory symptoms.

Distinct Clinical and Laboratory Patterns of Pneumocystis jirovecii Pneumonia in Renal Transplant Recipients

“…We observed an increase in serum calcium in the PcP cohort that was not present in the non-PcP cases. This finding has been previously described in PcP, interestingly, mainly in RTRs [26]. Moreover in a large PcP cohort in France, hypercalcemia at PcP diagnosis was associated with less fever [26].…”

“…This finding has been previously described in PcP, interestingly, mainly in RTRs [26]. Moreover in a large PcP cohort in France, hypercalcemia at PcP diagnosis was associated with less fever [26]. While this mechanism is unclear, increased serum calcium could be related to elevated 1,25dihydroxyvitamin D levels in PcP [11,17].…”

“…Respiratory distress was more pronounced in PcP compared to non-PcP, potentially reflecting the bilateral diffuse alveolar damage [11,24]. Interestingly, fever was only present in around one third of PcP cases, lower than historically reported but in line with recent larger studies exploring clinical symptoms of PcP pneumonias in RTRs [8,9,25,26]. Unspecific and atypical symptoms can contribute to the clinical challenge of distinguishing PcP from other pathologies involving the respiratory tract, including non-infectious causes [11].…”

Hypercalcaemia in an immunocompromised patient: consider Pneumocystis jirovecii pneumonia

“…PJP is known to form granulomatous tissue, with granulomatous tissue shown to cause hypercalcaemia through extrarenal production of 1,25‐dihydroxyvitamin D in diseases such as sarcoidosis and tuberculosis 4,5 . From case examples and comparisons with these other granulomatous diseases, it has been deduced that hypercalcaemia in PJP is also due to ectopic 1,25‐dihydroxyvitamin D production 4,5 . Hypercalcaemia associated with granulomatous disease generally responds well to treatment with corticosteroids 5 …”

“…In a retrospective study of 49 transplant patients with established PJP, 12.2% presented with only generalised decline, without fevers or respiratory symptoms. Furthermore, 37% of patients were hypercalcaemic, with these patients more likely to present with isolated general decline 4 …”