Rare Cause of Non-PTH Mediated Hypercalcemia Due to Pneumocystis Pneumonia in Renal Transplant Recipient

Introduction:
Hypercalcemia secondary to persistent hyperparathyroidism is common in kidney transplant recipients (KTR). We report a rare cause of non-PTH mediated hypercalcemia in KTR due to pneumocystis jirovecii pneumonia (PJP). The incidence of PJP in KTR is 5-15% in absence of antibiotic prophylaxis. Incidence of hypercalcemia in KTR with PJP is unclear, but scattered case reports are found in literature. The proposed mechanism for hypercalcemia is an infectious granulomatous reaction. PJP induced hypercalcemia needs to be considered in KTR patients with non-PTH mediated hypercalcemia.

Case Description:
A 62-yr-old male with kidney transplant for renal failure from glomerulosclerosis, three years prior to presentation was admitted for dyspnea and fever. Imaging showed bilateral lung infiltrates, concerning for multifocal infection. Considering his imaging findings and elevated Beta D glucan levels, he was empirically started on PJP treatment with atovaquone on day 4 of admission. Bactrim was not used due to acute renal failure. On day 1, calcium was 10 mg/dL (8.4-10.4), which then progressively increased from 10.7 mg/dl on day 4 to a peak calcium level of 14.4 mg/dL on day 12. Further work up showed PTH: 4.7 pg/mL (12-88), PTHrP: 0.6 pMol/L (< /= 4.2), Vitamin D 1, 25: 198 pg/mL (18-72), Vitamin D 25: 79 ng/mL (20-100), SPEP: no M spike, UPEP: no M spike but had a lysozyme band suggestive of granulomatous infection, other fungal studies negative, normal thyroid levels, AFB culture negative. On day 12, he was started on prednisone 60mg presuming hypercalcemia from PJP. On day 13, calcium improved to 11.7 mg/ dL, but his renal function worsened requiring hemodialysis (HD). On day 14, he had respiratory failure requiring intubation and underwent bronchio-alveolar lavage (BAL) which was positive for pneumocystis PCR. He was started on bactrim on day 17 and continued on high dose steroid. By day 19, he was extubated, renal function stabilized without HD and calcium normalized to 8.9 mg/dL. Unfortunately, he had gastrointestinal bleed and refused further procedures eventually opting for hospice on day 23.

Discussion:
PJP is a common opportunistic infection in immunosuppressed patients like KTR. The advent of prophylaxis has significantly decreased the incidence of PJP in KTR to 0.3%-2.6%. PJP in KTR is sometimes associated with hypercalcemia. Prevalence of hypercalcemia in KTR with PJP is unclear, but as per a hospital based retrospective study (Hamroun et al., 2019), 37% of PJP patients in KTR (18/49) had hypercalcemia that preceded pneumonia/findings on imaging. The proposed mechanism for hypercalcemia is granulomatous in nature, due to increased extra renal production of 1 alpha hydroxylase enzyme from increased macrophage recruitment in lungs to clear pneumocystis organisms. Hypercalcemia resolved after completion of treatment and resolution of PJP. High dose steroids can be used as hypercalcemia is mediated by a granulomatous reaction. It is crucial for physicians to have a high index of suspicion for PJP as the etiology of pneumonia in immunocompromised organ transplant recipients with non- PTH mediated hypercalcemia, thus ensuring timely diagnosis and treatment.